Downregulation of increased CD95 (APO-1/Fas) ligand in T cells from human immunodeficiency virus-type 1-infected children after antiretroviral therapy.
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Biomedical subjects
Publications and source records attributed to J Haas.
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Sequences of a new herpesvirus with homology to gammaherpesvirinae were recently identified in AIDS-associated Kaposi's sarcoma (KS). Subsequently this novel virus, called KS-associated virus (KSHV) or human herpesvirus (HHV) 8 was detected in classical KS and AIDS-associated body cavity based lymphomas by polymerase chain reaction. In this report major and minor capsid proteins of HHV-8 were molecularly cloned and produced as recombinant proteins in Escherichia coli. Sera from 69 HIV-1 infected patients with KS, 30 HIV-1 infected patients without KS and 106 control individuals were tested by enzyme-linked immunosorbent assay for anti-HHV-8 capsid IgM and IgG antibodies. Sera from four patients were tested over periods ranging from 18 months to 6 years. IgG antibodies directed against HHV-8 capsid antigens were detected in patients with AIDS-associated KS and in some AIDS patients without KS. Seroconversion with IgM and IgG antibodies directed against HHV-8 capsid proteins occurred more than 1 year prior to diagnosis of KS. In a considerable portion of KS patients no IgM or IgG antibodies against HHV-8 capsid proteins were detected. In these patients there was an inverse relationship between antibodies against HHV-8orf26 and the CD4/CD8 ratio, suggesting that the inconsistency of anti-HHV-8orf26 antibodies is due at least partly to an impaired immune response. No reactivity against HHV-8 capsid antigens was detected in the vast majority of sera from HIV-negative control individuals. Our findings indicate that a specific humoral immune response against capsid proteins is raised in HHV-8 infected individuals, and that anti-capsid antibodies can be used to diagnose HHV-8 infection. The correlation between occurrence of anti-HHV-8 antibodies and KS supports the hypothesis of a causative role of HHV-8.
Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains difficult to diagnose, particularly since structural abnormalities may not be revealed by magnetic resonance imaging (MRI). Glucose utilisation was measured by positron emission tomography (PET) in 35 SLE patients to detect signs of CNS involvement. The patients were examined by a standardised neurological examination, a battery of tests to evaluate neuropsychological performance and MRI. Antineuronal antibodies were determined to investigate their putative role in CNS involvement in SLE. Twenty patients had distinct neurological (17) and/or psychiatric (3) symptoms. Ten patients had pronounced cognitive impairment. Neurological and cognitive deficits were thus found to be unrelated disorders in SLE. Global glucose utilisation of SLE patients did not differ significantly from that of normal controls, nor were differences found between SLE patients with or without neurological or cognitive abnormalities. On MRI of the brain, the number and size of white matter lesions correlated with the presence of neurological deficits but were unrelated to the severity of cognitive impairment. Within the normal range, lower global glucose utilisation tended towards lower values with increasing number and size of white matter lesions. Patients with lesions larger than 8 mm also showed distinctly increased IgG anticardiolipin antibody titres, whereas measuring antineuronal antibodies did not reveal any relation to the variables investigated. We conclude that the demonstration of CNS lesions by MRI can contribute confirmatory evidence for CNS involvement in SLE, but PET or the presence of antineuronal antibodies adds little if any information beyond that obtained by clinical examination, neuropsychological testing, and MRI.
The inadequacy of clinical methods has spurred efforts to develop objective, measurable and reproducible parameters for the spread and growth behaviour of cervical cancer. Morphological methods were applied first. They can be used only on the surgical specimen, but are accessible to biometry. The presented results are based on 479 surgical specimens obtained at radical abdominal hysterectomy for cervical cancers of different sizes. The specimens were processed as frontal giant sections with the cervix, the vaginal cuff and the parametria on both sides. The median follow-up time was 7-8 years. Statistical correlations were found between follow-up data, biometric morphologic criteria and survival. The statistical ranking of the significant prognostic factors produced the following order: lymph node metastases, size of lymph node metastases, tumour volume, parametrial involvement and vascular invasion.
The relationship between neuropsychological impairments and changes in cranial MR images was investigated in a group of 74 consecutive patients with the sporadic form of amyotrophic lateral sclerosis (ALS). Neuropsychological tests included measures of frontal lobe function, memory, intelligence, and attention. Compared with a control group, a significant impairment of the ALS group emerged for the areas of visual attention, inhibition of response alternatives, visual memory, and word generation. These neuropsychological impairments did not show a relation to clinical status of the patients. Likewise, MR parameters derived by computer assisted planimetric analysis showed a ventricular enlargement and parenchymal atrophy in the ALS group compared with age-matched controls. When ALS patients were assigned to two subgroups differing on the basis of the neuropsychological tests by cluster-analysis the cluster with the significant impairment also showed a pronounced change for the MR-parameters while the subgroup showed essentially normal neuropsychological performance. This pattern suggests that subgroups of ALS with differential impairment of neuropsychological functions can be defined.
In order to investigate the role of Helcococcus kunzii as a colonizer of skin and as a possible participant in diabetic foot ulcers, we used a selective medium to culture both lower- and upper-extremity skin from a study group of podiatry patients (60 diabetics and 60 nondiabetics) and a control group of 50 healthy volunteers. Although differences in colonization were not statistically significant, a trend toward higher colonization rates in the group of podiatry patients was noted. H. kunzii appears to preferentially colonize the skin of the feet, and while its pathogenic role in diabetic foot ulcers is difficult to establish, it may be a previously unrecognized component of the polymicrobial flora characteristically isolated from patients with these infections.
OBJECTIVE: The aim of the study was to prove the sensitivity of sonographic measurements for the presence of a fetal hyperinsulinism. METHODS: In a longitudinal examination of 102 insulin-dependent diabetics we show the correlation between the amniotic fluid insulin level and the biparietal diameter, abdominal diameter and femur length in the third trimester. The control of the maternal metabolic state was done by measuring the glycosylated hemoglobin and fructosamine at the time of the amniocentesis. RESULTS: The sensitivity, specificity, positive and negative predictive value of sonographic measurements > 75th percentile in fetal hyperinsulinism was for the biparietal diameter 21, 96, 81 and 62%, for the abdominal diameter 48, 82, 69 und 66%, and for the femur length 22, 90, 67 and 57%. The maternal glycoproteins did not show any correlation with the amniotic fluid insulin level. CONCLUSIONS: The results demonstrate that fetal hyperinsulinism cannot be proved by fetal biometry or evaluation of the maternal metabolic state.
Rapid degradation of prostacyclin (PGI2) inherent to its molecular structure has long been a major limitation in assessing the natriuretic effect of this prostaglandin. The recent availability of the stable PGI2 analogue iloprost now allows for a comparative study with prostaglandin E2 (PGE2). In the present study conducted in six anesthetized dogs, the intrarenal effects of two consecutive doses (1 and 4 ng x kg(-1) x min(-1)) of PGE2 on renal blood flow, glomerular filtration rate, and urinary sodium excretion were compared with the effects of two identical doses of iloprost. The selected doses of PGE2 were those producing a maximal natriuretic and vasodilator response without affecting mean arterial pressure. A washout period was allowed between administration of PGE2 and iloprost. PGE2 infusion significantly increased fractional sodium excretion from 0.69+/-0.1 to 2.79+/-1.1% and 4.27+/-1.2%% (P<.05), respectively. These changes in fractional sodium excretion induced by PGE2 were associated with significant increases in renal blood flow from 151.1+/-62 to 185+/-64.3 and 185.6+/-64.3 mL/min (P<.05), respectively; however, no significant alterations were seen in glomerular filtration rate, from 29.5+/-9.4 to 35.2+/-12.2 and 32.7+/-7.8 mL/min (NS), and mean arterial pressure, from 117.6+/-26 to 113.9+/-24.1 and 112.3+/-24.1 mm Hg (NS) during control and PGE2 infusion. At identical doses, sequential infusion of PGI2 had no effect on renal blood floww and glomerular filtration rate, producing natriuresis only at the highest dose, a fractional sodium excretion from 0.69+/-0.1 to 0.8+/-0.28 mm Hg (NS) and 1.05+/-0.34% (P<.05), respectively. In conclusion, the present study confirms that PGE2 exerts a natriuretic effect during increases in renal blood flow. In contrast, PGI2 had no hemodynamic effect, and the natriuresis was markedly blunted.
We present the design of a double-blind, randomised placebo-controlled phase III study to evaluate safety and efficacy of IVIG in the treatment of patients suffering from primary or secondary chronic progressive multiple sclerosis. The primary endpoint is disability. Two measures of disability were chosen in order to assess the primary end point (a) sustained improvement (assessed at month 6, confirmed at month 9) and (b) progression to increasing disability of the disease (sustained for 3 months) at any time during the course of this 2 years study. The disability is measured by the Extended Disability Status Scale (EDSS). Secondary end points include the assessment of visual function, functions of the upper extremity, cognitive functions, depression and quality of life.
We used a nested polymerase chain reaction assay to quantitate the number of viral copies in cells of CSF of eight patients with herpes simplex virus encephalitis (HSVE). The viral load was monitored in serial CSF samples during the course of disease and correlated to clinical symptoms, radiologic manifestations, efficacy of acyclovir treatment, and overall clinical outcome. Before treatment, HSV type 1 (HSV-1) copies were detected at a mean value of 1,786/10(5) (range, 5 to 8,333/10(5) cells; median, 81/10(5) cells). During therapy, HSV-1 DNA decreased gradually to a mean value of 6 copies/10(5) cells (range, 0 to 33 copies/10(5) cells; median, 0 copies/10(5) cells) within 6 to 21 days and disappeared or was barely detectable before treatment completion in most cases. The HSV-1 burden in the CSF did not clearly correlate with the severity of clinical signs or the degree of cranial imaging findings and overall outcome. Quantitation of HSV-1 copies allows rapid and reliable monitoring of antiviral therapy. The absence of a clear correlation between viral load in the CSF and morbidity may suggest a role for indirect mechanisms of brain injury in HSVE.
OBJECTIVE: To compare expectant management with local instillation of 50% glucose solution for tubal pregnancies with a serum hCG level < or = 2500 mIU/mL. DESIGN: Prospective, non-randomized, comparative clinical study. SETTING: Two university departments. PATIENTS: One hundred and twenty-eight patients with laparoscopically-confirmed tubal pregnancy and serum hCG < or = 2500 mIU/mL. INTERVENTIONS: Eighty patients in Graz were treated with laparoscopic instillation of 50% glucose solution and 48 patients in Turku were followed expectantly. MAIN OUTCOME MEASURES: Resolution of hCG excretion, need for further interventions. RESULTS: Seventy-four of the 80 patients (92%) in the glucose group (32 of 33 with an initial hCG < or = 250 mIU/mL and 42 of 47 with hCG 251-2500 mIU/mL) and 36 of 48 (75%) patients in the expectant group (19 of 23 with an initial hCG < or = 250 mIU/mL and 17 of 25 with hCG 251-2500 mIU/mL) had resolution of the pregnancy with no further intervention (p=0.008, chi-square test, odds ratio 0.24). CONCLUSIONS: Glucose instillation is superior to expectant management for patients with early tubal pregnancy.
The following article reports on an analysis of 257,064 medical examination data provided by the German Industrial Engineering and Traffic Safety Control organization, a service of industrial medicine. In addition to the occurrence of diseases (ICD-classification), correlations between the age, sex, nationality and occupations (ILO-classification) are shown, including occupational importance and need for continuing medical treatment. It could be demonstrated that there are different areas of regarding diseases when comparing foreign and German workers, based on places of work, and on social and cultural factors.
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A structured mathematical model describing the dynamics of hybridoma growth and monoclonal antibody (mAb) production in suspension cultures is presented. The model fits well to experimental data obtained from batch, fed-batch, and continuous cultures with hybridoma cells. Applications of the model for process control are demonstrated. 1. An extended Kalman filter (EKF) was designed to estimate the state of the process. The oxygen consumption rate of the cell culture is monitored on-line and is used as the only measurement information for the EKF. This EKF is able to provide good estimates for living and dead cell densities and the medium composition. 2. The mathematical model can be applied for the optimization of fed-batch cultures.
BACKGROUND: The expression of both the env and gag gene products of human immunodeficiency virus type 1 (HIV-1) is known to be limited by cis elements in the viral RNA that impede egress from the nucleus and reduce the efficiency of translation. Identifying these elements has proven difficult, as they appear to be disseminated throughout the viral genome. RESULTS: Here, we report that selective codon usage appears to account for a substantial fraction of the inefficiency of viral protein synthesis, independent of any effect on improved nuclear export. The codon usage effect is not specific to transcripts of HIV-1 origin. Re-engineering the coding sequence of a model protein (Thy-1) with the most prevalent HIV-1 codons significantly impairs Thy-1 expression, whereas altering the coding sequence of the jellyfish green fluorescent protein gene to conform to the favored codons of highly expressed human proteins results in a substantial increase in expression efficiency. CONCLUSIONS: Codon-usage effects are a major impediment to the efficient expression of HIV-1 genes. Although mammalian genes do not show as profound a bias as do Escherichia coli genes, other proteins that are poorly expressed in mammalian cells can benefit from codon re-engineering.
UNLABELLED: In a prospective, randomised, open trial 103 term newborns with persisting dyspnoea, tachypnoea and/or cyanosis were treated with oxygen for 5-10 min and then with oxygen plus mask continuous positive airway pressure (CPAP) for another 5-15 min. Cases with overt prenatal or intrapartum obstetric pathology had been excluded from the study. Forty-one infants (40%) responded to this procedure within 10-25 min. The remaining 62 infants (60%) were randomly allocated to one of three forms of further treatment: continuation of mask CPAP for 20 min (group A, n = 24), volume expansion with 9 ml of 3 ml albumin, 3 ml glucose, and 3 mEq of sodium bicarbonate (group B, n = 24), or volume expansion with 4.5 ml albumin and 4.5 ml glucose (group C, n = 14). There was no statistical difference in birth weight, gestational age or Apgar scores at 1 and 5 min between the infants of the groups. Time to normalisation of symptoms was significantly shorter in the volume expansion groups (B: 45 +/- 41 min, range 20-180, and C: 80 +/- 72 min, range 20-210) than in the mask CPAP group (A; 224 +/- 256 min, range 30-1200, P = 0.02). There were statistical differences in umbilical cord and capillary pH values among the infants of the three groups, but the response to therapy was not related to the degree of acidaemia. Thirty-four infants (33%) who did not respond were admitted to a special care unit for further examination (group A: 21/24, group B: 7/24; group C: 6/14). Of these, 23 had no abnormal findings, 8 infants had radiological signs of transitory respiratory distress, and 1 had a non-tension pneumothorax. Septicaemia was found in two infants. No infant was intubated. At discharge all 103 infants did well. CONCLUSION: Incremental application of simple primary care procedures including volume expansion (with or without alkali) in term newborns with persisting postnatal tachypnoea and dyspnoea helps avoid overtreatment and unnecessary separation from the mothers in most cases and reliably selects infants who need close monitoring or special treatment.
OBJECTIVE: To determine the accuracy of reflection pulse oximetry and visual on-line signal identification during the second stage of labor. STUDY DESIGN: The reflection pulse oximetry system used allows visual on-line identification of valid signals by showing the original red and infrared signals. With this system oxygen saturation measurements are averaged over nine heartbeats only. An atraumatic suction probe was used. The measurements of the last 10 minutes before delivery were compared with umbilical venous cord blood samples taken soon after delivery. RESULTS: The correlation between reflection pulse oximetry readings during the last 10 minutes before delivery and umbilical vein oxygen saturation was significant (r = 0.45; p < 0.0005). Standard regression analysis showed R2 of 0.45. This did not change if weighted by the rate of valid signals (R2 = 0.42). If the predelivery loss of valid signals was less than 5 minutes, the correlation improved (r = 0.47, p < 0.001). Umbilical vein pH did not correlate with pulse oximetry readings. CONCLUSION: The reflection pulse oximetry system used allows visual on-line identification of even short periods of valid signals and reflects actual oxygen saturation in fetal arterial blood.
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