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Biomedical subjects

E Laine

Publications and source records attributed to E Laine.

At least 37 records · Page 2Linked to original sources
PubMed1995

Changes in solid-state structure of cyclophosphamide monohydrate induced by mechanical treatment and storage.

The effects of mechanical treatment and various storage conditions on the structure of cyclophosphamide monohydrate were evaluated by thermal and X-ray analyses and molecular modeling. The monohydrate form of cyclophosphamide was found to convert to the anhydrous form through a metastable phase. Metastable forms were produced by mechanical treatment and by desiccation. These forms could be detected in differential scanning calometric thermograms as endothermic peaks, at approximately 39 degrees C, and X-ray powder diffractometric analysis, e.g.; by a characteristic reflection at 15.3 degrees (2 theta). Molecular modeling was used to study molecular interactions and putative metastable structures. The dehydration enthalpies of the cyclophosphamide monohydrate obtained from quantum chemical calculations and DSC analysis were 51.6 and 36.1 J/g, respectively. In a unit cell of the stable monohydrate, a water molecule is held by O(7) of the cyclophosphamide molecule and N(6)H of a neighboring cyclophosphamide molecule, with hydrogen bonds enabling existence of a water tunnel. The metastable form of cyclophosphamide is detected when a sterically formed block in the possible tunnel is removed, and the water molecules are allowed to leave the system one by one.

Calorimetry, Differential Scanning↗
PubMed1995

Role of virus and host variables in virus persistence or immunopathological disease caused by a non-cytolytic virus.

C57BL/6 mice infected with increasing doses of the Armstrong isolate of lymphocytic choriomeningitis virus (LCMV) or a variant Cl 13-Armstrong, derived from LCMV-Armstrong, exhibited distinct phenotypes with respect to clearance of virus and to cytotoxic CD8+ T cell (CTL)-dependent immunopathological disease. Low (10(2) p.f.u.) and high doses (10(7) p.f.u.) of LCMV-Armstrong were cleared rapidly from immunocompetent mice. Inoculation of a high dose (10(7) p.f.u.) of LCMV Cl 13-Armstrong temporarily induced a partial deletion of the antiviral CTL precursors (CTL-p) leading to chronic infection in several organs. Although virus was cleared from most organs by day 90-150 post-infection, it persisted in the kidney. The few remaining CTL-p were able to expand and eventually clear the virus. Systemic viral titres correlated inversely with the number of CTL-p. However, in contrast LCMV-Docile injected at high dose was able to cause complete exhaustion of CTL-p resulting in long term viral persistence. LCMV-Aggressive, derived from the same parental LCMV-WE (UBC) as Docile, showed a phenotype comparable to wild-type virus. Doses of < 10(7) p.f.u. of both Armstrong virus and of Cl 13-Armstrong failed to exhaust CTL-p and caused lethal CD8+ T cell-dependent choriomeningitis and a substantial footpad swelling after local infection. By contrast, doses > 10(3) p.f.u. of LCMV-Docile failed to cause lethal choriomeningitis in C57BL/6 mice. When Cl 13-Armstrong virus (but not LCMV-Armstrong) was injected intravenously in addition to intracerebrally or into the foot, the local immunopathology was abrogated in a dose-dependent fashion. The suppression of immunopathology paralleled the extent of exhaustion of the specific CD8+ T cell response. Nucleotide sequence analysis of the viral S-RNA fragments coding for CTL epitopes in H-2b mice revealed an asparagine to serine change of amino acid 280 in the CTL epitope 275-286 of the LCMV-Docile glycoprotein (GP) in comparison to LCMV-Aggressive or wild-type WE. This change reduced overall CTL activity and thereby probably contributes to exhaustion of CTL responses in C57BL/6 (H-2b) mice. Thus, local versus systemic antigen distribution, viral characteristics and immunological parameters determine induction and exhaustion of CD8+ T cells and the course and extent of immunopathological disease.

Amino Acid Sequence↗
PubMed1994

Resistance of lymphocytic choriomeningitis virus to alpha/beta interferon and to gamma interferon.

The susceptibility to alpha/beta interferon (IFN-alpha/beta) or to gamma interferon (IFN-gamma) of various lymphocytic choriomeningitis virus (LCMV) strains was evaluated in C57BL/6 mice and in various cell lines. Anti-IFN-gamma treatment in vivo revealed that the LCMV strains Armstrong, Aggressive, and WE were most susceptible to IFN-gamma whereas Traub, Cl 13-Armstrong, and Docile were resistant. The same pattern of susceptibility to recombinant IFN-gamma was observed in vitro. In vivo treatment with anti-IFN-alpha/beta showed a sizeable increase in replication of Aggressive, Armstrong, and WE; effects were less pronounced for Docile, Cl 13-Armstrong, or Traub. Correspondingly, WE, Armstrong, and Aggressive were all relatively sensitive to purified IFN-alpha/beta in vitro, and Cl 13-Armstrong, Docile, and Traub were more resistant. Overall, there was a good correlation between the capacity of LCMV strains to establish a persistent infection in adult immunocompetent mice and their relative resistance to IFN-gamma and IFN-alpha/beta.

Animals↗
PubMed1993

Peripheral clonal deletion of antiviral memory CD8+ T cells.

Antiviral cytotoxic memory CD8+ T cells adoptively transferred to mice which are persistently infected with lymphocytic choriomeningitis virus WE or DOCILE initially proliferated extensively; they either caused the death of the recipient or, alternatively, disappeared within a few days. Apparently, the complete and coordinated induction and stimulation by widely distributed viral antigen caused these memory T cells to die before virus had been eliminated from the host. Thus memory T cells are as susceptible to peripheral exhaustion/deletion as unprimed T cells. These results indicate possible limitations of exclusively CD8+ T cell-mediated adoptive immunotherapy against viral infections or tumors.

Animals↗
PubMed1992

Resistance to influenza virus infection of Mx transgenic mice expressing Mx protein under the control of two constitutive promoters.

Transgenic mice constitutively expressing in the brain the influenza virus resistance protein Mx1 controlled by the HMG (3-hydroxy-3-methylglutaryl coenzyme A reductase) promoter showed specific resistance against the neurotropic influenza A virus strain NWS. Control mice of the A2G strain express Mx1 protein in all organs, but only after induction by interferon type I upon or without viral infection. The extent of specific resistance in transgenic mice of the best-expressing line reached about two-thirds that of controls, most likely because of considerably less total-body Mx protein activity in the transgenic mice. Thus, the theoretical advantage in these mice of the continuous presence of Mx protein with early inhibitory potential to viral replication was apparently offset by restricted organ expression. Strong evidence that the Mx1 protein on its own is a specific anti-influenza A virus agent and that its efficiency in the experimental setting is independent of interferon actions could be derived from the treatment of experimental and control mice with anti-interferon antibodies at the time of virus tests. Whereas in A2G mice, Mx1 mRNA and Mx1 protein synthesis were abolished and viral resistance was markedly reduced or abolished, resistance in the transgenic mice persisted to almost the same degree. Transgenic mice generated with a mouse albumin/Mx1 cDNA construct showed liver-specific expression. However, in two expressing transgenic lines, Mx1 protein synthesis was suppressed after a few months. The mechanism of suppression could not be elucidated, but increasing methylation of the transgene's coding region was not the cause. It is possible that continuous Mx1 protein expression in the liver is less well tolerated than that in the brain. Whether this partial suppression and, with the HMG promoter, restricted organ expression are the organism's responses to interference of Mx1 with normal cellular activities such as nucleocytoplasmic transport of RNA and proteins cannot be determined until the molecular mechanisms of antiviral activity of Mx1 protein are understood.

Animals↗
PubMed1992

[Novel possibilities for treatment of parkinsonian tremor and other abnormal movements by stimulation of the nucleus ventralis intermedius thalami].

Chronic thalamic stereotactic stimulation has been performed in 22 patients with disabling tremor and poor response to drug therapy: 17 parkinsonian tremors and 5 essential tremors. Our first results are presented with a mean follow-up of 26 months. Parkinsonian tremors 17 = complete disappearance: 12, clear improvement: 5. Essential tremors 5 = complete disappearance: 3, clear improvement: 1, failure 1 cured by thalamotomy. Choreic or ballistic dyskinesias 7 = complete disappearance: 5, clear improvements: 2. Dystonic dyskinesias 3 = complete disappearance: 2, failure: 1. This new stereotactic procedure permits to control easily not only tremor but also L-Dopa induced dyskinesias: choreic or ballistic dyskinesias and biphasic dystonic dyskinesias. The place of this surgical treatment among the other therapeutic possibilities is discussed.

Electric Stimulation Therapy↗
PubMed1991

The causes of hospital-treated acute lower respiratory tract infection in children.

OBJECTIVE: To determine the etiologic agents in children with acute lower respiratory infection. DESIGN: A survey of a series of patients. SETTING: General pediatric hospital serving an urban population with and without referrals in Helsinki, Finland. PARTICIPANTS: 135 Finnish children aged 2 months to 15 years (mean, 1.75 years), with clinically defined acute lower respiratory infection (with difficulty of breathing), or found to have fever and a pneumonic infiltrate on chest roentgenogram. SELECTION PROCEDURES: Consecutive sample on voluntary basis. INTERVENTIONS: None. MAIN RESULTS: Of 121 children with adequate samples, an etiologic diagnosis could be established in 84 (70%): 30 (25%) had bacterial, 30 (25%) viral, and 24 (20%) mixed infections. Antibody assays alone identified the agent in 91% of positive cases. CONCLUSIONS: Bacterial infections are common but generally underestimated in acute lower respiratory infection; serologic methods add significantly to their detection.

Acute Disease↗
PubMed1991

Serum tumor necrosis factor-alpha concentrations in children hospitalized for acute lower respiratory tract infection.

Tumor necrosis factor-alpha (TNF alpha) concentrations were measured by radioimmunoassay in sera of 118 children (median age, 1.7 years; range, 2 months-15 years) hospitalized for acute lower respiratory tract infection (ALRI). Both viral and bacterial ALRI were associated with elevated concentrations of TNF alpha. Concentrations greater than 40 ng/l were seen in children with bacterial or mixed ALRI in 64% and with viral ALRI in 50% of cases. Elevated concentrations were associated with longer duration of fever before admission (P less than .05) and with a higher serum C-reactive protein concentration (P less than .05). There were no significant differences in TNF alpha concentrations between gram-positive and gram-negative infections, nor was there an association with clinical severity of ALRI. TNF alpha concentrations decreased in most patients to normal within 5 days of hospitalization, irrespective of the etiology of the infection.

Acute Disease↗
PubMed1985

[Acute transient Korsakoff's syndrome caused by hematoma of the floor of the 3rd ventricle].

A forty four year-old woman had had an amenorrhea-galactorrhea syndrome for 3 months when a Korsakoff's syndrome with headache suddenly appeared. Neuroradiological investigations revealed a hematoma involving the anterior part of the IIIrd ventricle. After a short period of neurogenic hypernatremia the lesion disappeared with the development of a spontaneous ventriculocisternostomy. Simultaneously, the Korsakoff's syndrome decreased until it went off almost completely, but a diabetes insipidus appeared and the hyperprolactinemia remained unchanged. Four years later, those are the only symptoms which are still present. This case, particular by its aetiology and evolution, illustrates well the possibility of functional Korsakoff's syndromes.

Acute Disease↗
PubMed1982

[Total right hemispherectomy: neurophysiological study after twenty-six years].

Twenty-six years after a total right hemispherectomy for tumor when thirteen years old, a right-handed patient presented with disturbances of equilibrium, urinary incontinence, and a marked reduction in motor impulses, in spite of a subnormal intelligence quotient (0.85). Computed tomography examinations suggested the presence of a normal pressure hydrocephalus. However intracranial pressure monitoring and isotopic and cerebrospinal fluid perfusion tests showed the absence of any cerebral obstruction, and free communication between the cerebral and spinal spaces, though intracranial volume capacity accommodation was greatly reduced. Clinical examination demonstrated good quality sensory appreciation by the left half of the body, the possibility of detecting an object in the visual hemifield supposedly blind, and perfect location of a sound source. Somesthetic evoked potentials were studied by stimulating the median nerve in the left and right wrist regions. Left hemisphere evoked potentials from a contralateral stimulus, were of normal latency, amplitude and morphology, the response to an ipsilateral stimulus also presenting an early potential component (N 26 starting at N 21). This exceptional finding in a hemispherectomized patient could be related to activity of the spinoreticulothalamic tracts in the lemniscal or extralemniscal systems. Auditory function tests demonstrated perfect stereoaudiometry and the quality of perception during dichotic listening tests. Auditory evoked potentials in the brain stem included only minor functional-type anomalies, with slightly increased latencies in the pons on the left, and the mesencephalon and pons on the right. The presence of a bilateral wave VI was related to activity of the median geniculate pathway. Visual function tests showed good quality left photomotor reflexes and positive object detection in the anopsic hemifield. Results of these tests were reproducible during the same examination and after an interval of several months. The relevant literature is reviewed.

Adolescent↗
PubMed1981

[Arteriovenous malformations in deep cerebral area. Topographic classification. Therapeutic possibilities and results about 46 cases (authors' translation)].

The authors study the clinical dispositions of 46 arteriovenous malformations developed in deep cerebral area and detected in 41 cases by an haemorrhagic accident and after make a radiological classification. They class the M.A.V. of nucleus centralis with the localizations of the nucleus caudate's head, the insula and lentiformis nucleus and the capsulo thalamic area; the ventriculo-cisternalis M.A.V., the corpus callosum M.A.V. and complicated forms. With this classification they analyse the different operative technics that permit to obtain a complete extirpation in 26 cases about 39 operated patients. The results are excellent in 19 cases, good for 8 cases and mediocre in 4 cases. Eight patients are died during post operative time. The most important factors for the final result are the disturbance of consciousness before operative time and the malformations developed about several anatomical area. At last the authors insist on the fact that, if during next years, the embolism technics are not effective, the operation will be indicate in spite of the technical difficulties because the spontaneous evolution is always dangerous.

Adolescent↗
PubMed1980

[Fronto-orbital osteotomies for craniostenoses. 21 cases (author's transl)].

Three types of craniostenoses, plagiocephalies, trigonocephalies, and oxy-brachycephalies provoke modifications in the fronto-orbital region of the face, for which fronto-orbital remodelling osteostomies are proposed. Results obtained in 21 cases treated in this manner were very encouraging, as they were of good quality.

Craniofacial Dysostosis↗
PubMed1980

[Interest of the interthalamotrigonal appraoch to the third ventricle and pineal area's tumors (author's transl)].

The roof of the third ventricle is lying on the thalamus parts. When a tumor fills and expands the third ventricle it is always possible to lift up this velotrigonal roof like the cover of a box and to access to these lesions. The authors have approached 15 tumors of the third ventricle or pineal area by this route interthalamotrigonal about 78 cases of tumors operated in the Lille's neurosurgery department during 30 years. The technical possibilities are compared and the advantages of this route emphasized with usual access. The interthalamotrigonal access gives a great convenience during operation. It make easy the complete removal of removable tumors of the pineal area and the third ventricle. It is possible with minimum during operation and after effects for the patient.

Brain Neoplasms↗