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Biomedical subjects

A Brand

Publications and source records attributed to A Brand.

At least 127 records · Page 7Linked to original sources

In vitro fluence rate effects in photodynamic reactions with AIPcS4 as sensitizer.

It has been shown previously that the efficiency of photodynamic therapy (PDT) both in vivo and in vitro is dependent on fluence rate. In this study, different in vitro experiments showed that tetrasulfonated aluminum phthalocyanine (AIPcS4) is more efficient in photosensitization if the light is delivered at low fluence rate. Erythrocyte damage, virus inactivation and photooxidation of reduced glutathione (GSH) and histidine were all enhanced if light was delivered at 100 W/m2 as compared to 500 W/m2. Bleaching did not occur under these conditions. Oxygen depletion, shown to be important in fluence rate effects observed in vivo, does not seem to be involved. On theoretical grounds saturation of the triplet state is not likely under these conditions. A possible explantation for the observed fluence rate effects might be found in different reaction pathways, that are favored under high or low fluence rate illuminations. These reactions might involve uni- or bimolecular reactions of intermediate products, resulting in less efficiency at higher fluence rate. It proves to be important, under all circumstances, to monitor fluence rate, because a change in fluence rate, even with similar total fluences, might influence photobiological results in an unexpected way.

Erythrocytes↗

Primary targets for photoinactivation of vesicular stomatitis virus by AIPcS4 or Pc4 and red light.

Phthalocyanines are useful sensitizers for the photodynamic sterilization of red blood cell concentrates. The mechanism of photoinactivation of lipid-enveloped viruses is not completely understood. Vesicular stomatitis virus (VSV) was used as a model virus to study the primary targets of photoinactivation by aluminum phthalocyanine tetrasulfonate (AIPcS4) or silicon phthalocyanine HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc4) and red light. Inactivation conditions for VSV in buffer were determined using an end point dilution assay, and viral RNA synthesis in host cells was measured to determine the loss of infectivity in a direct way. The very rapid decrease in the viral RNA synthesis after photodynamic treatment was correlated with respect to different potential primary targets that are involved in different steps of the viral replication cycle. Damage to the viral proteins, induced by treatment with AIPcS4 or Pc4 and analyzed by gel electrophoresis, could not account for the observed loss of infectivity. Binding of VSV to host cells was only slightly impaired after photodynamic treatment with both sensitizers and could therefore not be responsible for the rapid decrease in viral RNA synthesis in cells. A very strong inhibition of viral RNA polymerase activity after treatment with AIPcS4 and red light was detectable using an in vitro assay. This decrease correlated well with the loss of infectivity, indicating that either the RNA or the viral RNA polymerase is the primary target for photoinactivation of VSV with AIPcS4. Treatment with Pc4 did not cause inhibition of viral RNA polymerase activity to an extent that could account for the observed very rapid loss of infectivity. It was therefore concluded that neither the viral proteins nor the binding to the host cells nor the RNA or RNA polymerase are the primary targets for photoinactivation of VSV by Pc4.

Animals↗

Immunomodulation and remyelination: two aspects of human polyclonal immunoglobulin treatment in immune mediated neuropathies?

Intravenous immunoglobulin is used in inflammatory demyelinating diseases of the peripheral as well as the central nervous system. It is not known which mechanism(s) accounts for the beneficial effect observed in these diseases. The immunomodulatory effects of IVIg in two different models of T and B cell activation were investigated. IVIg inhibited a predominantly cellular immune response of the Th 1 type, which was partially reversed by addition of Th 1 cytokines. In contrast, in a model, which leads to B cell differentiation and antibody production, a synergistic stimulatory effect of IVIg and Th2 cytokines was observed. The ability of IVIg to interfere with cell proliferation and to manipulate the Th1/Th2 profile will have consequences for the induction, character, and amplification of an immune response. Apart from the immunomodulatory effects, evidence shows that IVIg promote remyelination not only by abrogation of the auto-immune attack but also by an effect on glial cells. We showed that IVIg induce growth arrest of normal human fibroblasts and Schwann cells. In fibroblasts this growth arrest is accompanied by upregulation of GAS-3/PMP-22 mRNA. The implications of this finding are discussed. Further studies in human Schwann cells are imperative to prove the hypothesis that IVIg directly stimulates remyelination.

Autoimmune Diseases↗

Preinfection in vitro chemotaxis, phagocytosis, oxidative burst, and expression of CD11/CD18 receptors and their predictive capacity on the outcome of mastitis induced in dairy cows with Escherichia coli.

Four to 6 wk after parturition, 12 cows in second, fourth, or fifth lactation were experimentally infected in one gland with Escherichia coli. The capacity of chemotaxis, phagocytosis, oxidative burst, and expression of CD11/CD18 receptors to predict the severity of IMI was measured. Bacterial counts in the infected quarter, expressed as area under the curve, and residual milk production in the uninfected quarters were compared to determine severity of the infection. Although these two outcome parameters were highly negatively correlated, regression models with preinfection tests for leukocyte function fitted best with bacterial counts as an outcome parameter. Of the preinfection tests for leukocyte function, chemotaxis best predicted the outcome of the IMI that had been experimentally induced by E. coli. The number of circulating peripheral leukocytes just prior to inoculation was used to predict 52 and 45% of the severity of IMI for bacterial counts and residual milk production, respectively. As a categorical variable, parity predicted 75 and 56% of the severity of IMI expressed as bacterial counts and residual milk production, respectively. Because of the strong effect of parity on the outcome of the experimentally induced mastitis, analysis was performed to discriminate between second parity cows and older cows. Significant differences were found for the number of circulating peripheral leukocytes and for the expression of CD11b/CD18 and CD11c/CD18 receptors between younger and older cows.

Animals↗

Estimation of interdependence among quarters of the bovine udder with subclinical mastitis and implications for analysis.

Interdependency among udder quarters with subclinical mastitis was evaluated on 150 farms using a total of 35,828 udder quarters. The occurrence of high somatic cell count (SCC) (> 250,000 cells/ml) in 0, 3, and 4 quarters occurred at a higher rate than would be expected based on independence of the quarters. For all bacterial species, intramammary infection in 0, 2, 3, or 4 quarters of the same cow occurred at a higher rate than would be expected based on independence of the quarters. Intramammary infection and high SCC were found less often in front quarters than in rear quarters. High SCC and intramammary infection occurred more often in right front quarters than in left front quarters. High SCC in diagonal quarters occurred at a lower rate than expected. Corynebacterium bovis, Streptococcus agalactiae, and Staphylococcus aureus had the highest intraclass correlation within herd. Streptococcus uberis had a very low intraclass correlation within herd. The intraclass correlation within cow for the natural logarithm of SCC was 0.47. Corynebacterium bovis and Strep. agalactiae had the highest intraclass correlation within cow, and Streptococcus dysgalactiae had the lowest. Analytical methods were proposed to manage the problem of interdependence and its effect on the design or evaluation of field studies on subclinical mastitis.

Animals↗

Effect of natural infection with minor pathogens on susceptibility to natural infection with major pathogens in the bovine mammary gland.

OBJECTIVE: To evaluate the effect of natural udder infection with minor pathogens on subsequent natural infection with major pathogens. SAMPLE POPULATION: 7 dairy herds with low bulk milk somatic cell count. PROCEDURE: During a 20-month prospective study, milk samples were collected from diary cows at regular intervals and from quarters with clinical signs of mastitis. Incidence of intramammary infection was calculated in uninfected quarters and in quarters infected with minor pathogens. A within-cow, matched case-control analysis was used to evaluate the effect of minor pathogens on subsequent infection with major pathogens. RESULTS: Quarters infected with minor pathogens had higher somatic cell count than did uninfected quarters. In quarters infected with Corynebacterium bovis, the rate of infection with major pathogens was lower, whereas in quarters infected with coagulase-negative Micrococcaceae, the rate of infection with major pathogens was higher than that in uninfected quarters. From the within-cow comparison, it appeared that, in quarters infected with minor pathogens, infection with major pathogens was significantly lower than that in comparable control quarters not infected with minor pathogens. CONCLUSIONS: Minor pathogens have a protective effect against infection with major pathogens. The protective effect of C bovis against subsequent infection with major pathogens appears to be greater than the effect of coagulase-negative Micrococcaceae.

Animals↗

Metabolism of acetate in rat brain neurons, astrocytes and cocultures: metabolic interactions between neurons and glia cells, monitored by NMR spectroscopy.

The existence of metabolic compartmentation is generally accepted for the brain because of the specific differences in glial and neuronal metabolism. Extracellularly supplied acetate is believed to serve as a substrate only for glia cells, but not for neurons. To further test this hypothesis, primary rat brain cultures of neurons, astrocytes, and cocultures of both cell types were used to investigate the metabolic fate of [2-13C]acetate by means of nuclear magnetic resonance (NMR) spectroscopy. Acetate was metabolized by both cell types, neurons and astrocytes in culture. While glutamine was the main product of glial metabolism, labelled glutamate and aspartate were detected in neuron cultures. Astrocytes and neurons in cocultures showed a very different picture, which is similar to results obtained from brain slices, or in vivo studies. The analysis of the isotopomer pattern of glutamate and glutamine confirm an active glutamate-glutamine-cycle between neurons and astrocytes in cocultures. Furthermore, the analysis of unlabelled metabolites revealed a metabolic coupling of hypotaurine and taurine metabolism in astrocytes and neurons, which provides both cell types with one of the most important organic osmolytes.

Acetates↗

Evaluation of the effects of immunosuppressants on neuronal and glial cells in vitro by multinuclear magnetic resonance spectroscopy.

The use of the undecapeptide cyclosporine and the macrolide tacrolimus as immunosuppressants in transplantation medicine and for the therapy of immune diseases often provokes side effects, among the most important one is neurotoxicity. Changes in the cellular metabolism of glial cells (C6 rat glioma), neuronal cells (N1E-115 mouse neuroblastoma) and primary glia cells (isolated from rats) after addition of cyclosporine and tacrolimus were investigated using 1H-, 13C- and 31P-NMR spectroscopy in vitro. Cells were exposed to various concentrations of the drugs from 3 h to 42 days. The immunosuppressants (cyclosporine IC50 : 55 mumol/l; tacrolimus IC50 : 47 mumol/l) inhibited cell proliferation in a concentration- and time-dependent fashion. Multinuclear NMR studies of PCA extracts of drug-treated cells showed a significant deterioration in the energy status (a decreasing level of PCr : -46 +/- 11%; an increasing NDP/NTP ratio: +136 +/- 4% and an increasing level of Pi : +248 +/- 15%; mean +/- standard deviation). It also showed decreasing concentrations of major cell metabolites like NAA (-59 +/- 12%) in neuroblastoma cells and myo-inositol (-47 +/- 6%) in glia cells compared with untreated controls. Immunosuppressive treatment caused a large reduction of taurine (-36 +/- 12%) and glutamate (-68 +/- 10%) in all cell cultures, whereas intermediates of phospholipid biosynthesis (PE: +59 +/- 13%; PC: +127 +/- 27%;) and breakdown (GPE: +215 +/- 24%; GPC: +245 +/- 17%) increased. No significant differences were observed between the two immunosuppressants. The toxic effects of immunosuppressants on cell cultures are in line with MRI studies of brain oedema observed in patients under immunosuppressive treatment.

Animals↗

The influence of merocyanine 540 and protoporphyrin on physicochemical properties of the erythrocyte membrane.

The interaction of the red cell membrane with merocyanine 540 or protoporphyrin led to four phenomena, most probably interrelated. (i) The morphology changed from the normal discoid to an echinocytic form. This morphological change persisted when followed over a period of 24 h. (ii) Simultaneously, cell deformability was decreased, as revealed by viscosity measurements and a cell-filtration technique. (iii) Both drugs caused swelling of the erythrocytes in isotonic medium, due to a very-short-term increased permeability of the membrane, also for larger molecules such as lactose. The pathway of this temporary leak seems to be unrelated to the Na+/K+ -ATPase, the K+/Cl- and the Na+/K+/Cl- cotransport systems, the Ca2+-activated Gardos pathway, the oxidation/deformation-activated leak pathway and the so-called residual transport route. Despite the morphological changes, K+-leakage induced by mechanical stress was not increased. (iv) During osmotic swelling, the critical hemolytic volume was found to be increased in the presence of either merocyanine 540 or protoporphyrin. The increase critical volume protected erythrocytes against osmotic hemolysis.

Antiviral Agents↗

High-grade endometrial carcinoma in secretory endometrium in young women: a report of five cases.

Five cases of high-grade carcinoma occurring adjacent to secretory endometrium are described. One of the patients had the Lynch II syndrome, the others appeared to be sporadic. None of these cases appeared to be related to hyperestrogen. The presenting symptom in four was abnormal vaginal bleeding, and the other case was found incidentally in the course of investigations for infertility. There were delays in diagnosis due to the patients not seeking medical attention for abnormal bleeding, a reluctance of clinicians to perform dilatation and curettage, and difficulty in pathologic interpretation of the curettings. The interpretive problems related to extremely small volumes of tumor, difficulty in distinguishing carcinoma from menstrual endometrium, and difficulty in determining whether a carcinoma was endometrial rather or endocervical in origin. The tumors were aggressive, manifest by their high grade and stage. The importance of these cases is to impress upon clinicians and pathologists that endometrial carcinoma may occur in young women without any of the usual risk factors.

Adult↗

Vulvar Merkel cell tumor with glandular and squamous differentiation.

A case of a Merkel cell tumor of the vulva is presented. In addition to the typical microscopic, immunohistochemical, and ultrastructural features of Merkel cell tumor, there were areas of squamous and glandular differentiation. This is the ninth reported case of a vulvar Merkel cell tumor, and the first where squamous and glandular differentiation were seen. The findings support an origin of Merkel cell tumors from pluripotential stem cells.

Adenocarcinoma↗

Hypometric primary saccades of schizophrenics in a delayed-response task.

In this study, the execution of delayed saccades in 15 DSM-III-R-schizophrenic patients and 15 normal subjects was investigated. While looking at a central fixation cross, a peripheral target was randomly presented at 10 degrees eccentricity. Subjects were instructed to saccade to the target when the fixation cross was switched off after 500 ms. Two experiments were conducted: (a) a delayed-saccade task and, (b) a memory-guided saccade task, that is, the peripheral target was switched off together with the fixation cross. In the delayed-saccade task, amplitudes of regular saccades did not differ between schizophrenic patients and normals. In the memory-guided saccade task, schizophrenic subjects showed marked hypometric saccades. Incorrect delayed saccades (while the fixation cross was on) were also hypometric in schizophrenics, but not in normal controls. The final eye position, i.e., the position reached after the execution of correction saccades, however, did not differ between patients and controls. This means that schizophrenics show a deficit in the programming of primary saccades, if the fixation point and the peripheral target are (a) both visually presented or (b) both memorized. The results support the hypothesis that these saccades are the result of an averaging effect between the fixation point and the peripheral target. It is further hypothesized that these deficits might be explained by a lack of prefrontal inhibition of ocular fixation areas.

Adolescent↗

Hb Malmö [beta-97(FG-4)His-->Gln] leading to polycythemia in a Dutch family.

We have examined six individuals from a two-generation Dutch family for a suspected hemoglobin (Hb) abnormality. The propositus presented with polycythemia and complained of persistent weakness, headache, and epistaxis. All family members initially showed a normal Hb-electrophoretic pattern, but on isoelectric focusing, three of them displayed a fast-moving band associated with high packed red cell volumes (PCV) and increased red blood cell count. The Hb mutant was analyzed at the DNA level by specific gene fragment amplification (PCR), followed by direct DNA sequencing, and the mutation was confirmed by restriction enzyme analysis. We found a C-->G transversion (CAC-->CAG) at codon 97 of the beta-chain, which corresponded to the His-->Gln amino acid substitution previously described as Hb Malmö. We report here the clinical history of the patient, the effects of phlebotomy treatment, and the effect of subnormal iron conditions on the erythropoietic recovery after phlebotomy. The mechanism responsible for the induction of the higher oxygen affinity is discussed, as are some aspects concerning the occurrence, pathology treatment, and the genetic risk of Hb variants with high O2 affinity.

Adult↗

Antenatal care in pregnancies at risk of alloimmune thrombocytopenia: report of 19 cases in 16 families.

OBJECTIVE: To assess accuracy of a management program in patients at risk for alloimmune thrombocytopenia (NAITP) and to describe perinatal outcomes. STUDY DESIGN: Nineteen fetuses at risk of thrombocytopenia were identified using obstetric history, HLA type of the mother and fetal phenotyping in cases where paternal heterozygozity for the offending antigen was present. Cordocentesis was timed according to obstetric history and performed with safety precautions to prevent haemorrhage. High dose intravenous gamma globulin (IVIG) was administered to the mother in cases with a fetal platelet count < 100 x 10(9)/l. RESULTS: The platelet antagonisms were distributed as follows: HPA-1a in 15 patients, HPA-5a in two, HPA-3a in one, with one further woman who had antibodies against a private antigen. All multigravidas (N = 18) had previously given birth to an infant with NAITP and two of those infants had experienced severe bleeding. Two fetuses were negative for the offending antigen. The median and mean platelet count at first cordocentesis was 26 and 75 x 10(9)/l respectively (range 3-276). A total of 46 cordocentesis were carried out, of which 37 were followed by platelet transfusions. Bleeding complications were not observed. IVIG was administered to eight mothers and two fetuses responded. Nine infants were delivered by caesarean section (CS) and 10 vaginally at a mean gestational age of 37 weeks (range 34-41). The median and mean platelet count at birth was 141.5 and 140 x 10(9)/l, respectively (range 36-314). Ultrasound examination, both ante- and postnatally, revealed no intracranial haemorrhages. There was one procedure related neonatal death and one infant suffered from convulsions in the neonatal period due to a sinus thrombosis, possibly related to the platelet transfusions. CONCLUSIONS: When obstetric history is taken into account cordocentesis in NAITP can be postponed. Safety recommendations described in this study allow cordocentesis without bleeding complications. However, our study does not support routine cordocentesis in patients with a history of NAITP. Both the risks of cordocentesis, and the lack of prospective data on the magnitude of the risk of intrauterine or peripartal bleeding, should be considered.

Blood Transfusion, Intrauterine↗

Within day and between day variation of the in vitro under agarose chemotaxis assay in bovine.

The present study was conducted to determine within day variation (experiment I) and between day variation (experiment II) of the in vitro under agarose chemotaxis assay. Further, results from experiment II were used to estimate a more stable immunological parameter for the chemotactic activity. In experiment I, blood samples of eight cows were taken every 4 h starting at 0800 during a 24 h period. This procedure was replicated on three different days with peripheral white blood cells of lactating bovine. Chemotactic differential showed variation within a day. The differences between samplings were not constant over the days, but varied randomly from day to day. In experiment II, 12 cows were followed for 8 consecutive days and blood samples for chemotaxis assay were taken once a day at 0730. Differences between the days were significant. With a conditional auto regression model of the first order adjusted least squares means of each cow were estimated over the 8 consecutive days. The chemotactic value of a day was used to estimate the value of the next day. Expanding the model with more previous days did not improve the model. The results of this study indicate that blood samples for chemotaxis should be taken at the same time of the day to control for within day variation. If a sequence of chemotactic values is available we strongly suggest working with adjusted least square means of chemotactic differentials. These adjusted means show less random variation and are a more stable parameter for chemotactic activity.

Animals↗

Acute hypoglycemia masquerading as head trauma: a report of four cases.

Hypoglycemia, a commonly encountered metabolic emergency, is most often easily diagnosed and rapidly treated with satisfactory patient outcome. If not recognized and treated promptly, hypoglycemia may cause irreversible central nervous system injury; it rarely results in death. The classic presentation of hypoglycemia, a patient with diabetes mellitus on medical therapy (Insulin or oral hypoglycemic agents) who presents with an altered sensorium, is frequently seen in the emergency department (ED). Less often, patients with this metabolic emergency present to the ED in a manner suggestive of a situation other than hypoglycemia. Patients may present with seizure activity or focal neurological deficits, leading the physician to treat a primary neurological syndrome and not immediately recognize the primary cause of the problem. Alternatively, patients with hypoglycemia will present to the ED with an altered mental status after a traumatic event. The physician may again assume that the alteration in consciousness has resulted from a head injury and not a metabolic disorder. Four cases are presented in which the medical history of the event (i.e., trauma) suggested head injury as an explanation of the presentation when, in fact, hypoglycemia was responsible for the altered sensorium. The diagnosis of hypoglycemia is easily made with the performance of a bedside screening test which can be subsequently confirmed by laboratory blood analysis. It is imperative that emergency physicians consider hypoglycemia in all patients with any mental status abnormality, focal neurological deficit, or seizure activity, even when the findings seem to be explained initially by other etiologies.

Acute Disease↗