Biomedical subjects
Publications and source records attributed to G Franz.
Spathodea campanulata stem bark decoction (SCD) has shown hypoglycemic activity in mice. It was separated by column chromatography into different fractions, which were evaluated for their hypoglycemic, anticomplement and anti-HIV activities. The most polar fraction exerted by far the most prominent effect in different biological models.
Increasing evidence suggests that apolipoprotein D (apoD) could play a major role in mediating neuronal degeneration and regeneration in the CNS and the PNS. To investigate further the temporal pattern of apoD expression after experimental traumatic brain injury in the rat, male Sprague-Dawley rats were subjected to unilateral cortical impact injury. The animals were killed and examined for apoD mRNA and protein expression and for immunohistological analysis at intervals from 15 min to 14 days after injury. Increased apoD mRNA and protein levels were seen in the cortex and hippocampus ipsilateral to the injury site from 48 h to 14 days after the trauma. Immunohistological investigation demonstrated a differential pattern of apoD expression in the cortex and hippocampus, respectively: Increased apoD immunoreactivity in glial cells was detected from 2 to 3 days after the injury in cortex and hippocampus. In contrast, increased expression of apoD was seen in cortical and hippocampal neurons at later time points following impact injury. Concurrent histopathological examination using hematoxylin and eosin demonstrated dark, shrunken neurons in the cortex ipsilateral to the injury site. In contrast, no evidence of cell death was observed in the hippocampus ipsilateral to the injury site up to 14 days after the trauma. No evidence of increased apoD mRNA or protein expression or neuronal pathology by hematoxylin and eosin staining was detected in the contralateral cortex and hippocampus. Our results reveal induction of apoD expression in the cortex and hippocampus following traumatic brain injury in the rat. Our data also suggest that increased apoD expression may play an important role in cortical neuronal degeneration after brain injury in vivo. However, increased expression of apoD in the hippocampus may not necessarily be indicative of neuronal death.
A water-soluble fraction from the marine diatom Haslea ostrearia was capable to inhibit the in vitro replication of HSV-1 in Vero cells with 50% inhibitory concentration (EC50) of 14 micrograms/ml at a multiplicity of infection of 0.01 ID50/cells. In addition, this fraction delayed the HIV-1-induced syncitia formation on MT4 cells. At concentrations up to 200 micrograms/ml, no cytotoxicity was observed for both the Vero and MT4 cells. The fraction only inhibited the blood coagulation process at concentrations considerably exceeding the EC50.
BACKGROUND: The early post-traumatic vegetative state (VS) is compatible with recovery. Various clinical and laboratory tests have failed to predict recovery so we assessed the value of cerebral magnetic-resonance imaging (MRI) in prediction of recovery. METHODS: 80 adult patients in post-traumatic VS had cerebral MRI between 6 weeks and 8 weeks after injury. MRIs were reviewed by three neuroradiologists for the number, sizes, and location of brain lesions. Three neurologists assessed the patients at the time of MRI and at 2 months, 3 months, 6 months, 9 months, and 12 months after injury using the Glasgow Outcome Scale. FINDINGS: At 12 months, 38 patients had recovered while 42 patients remained in the VS. The demographic characteristics and causes and severity of injury were similar in patients in persistent VS (PVS) and those who recovered (NPVS). An average of 6.1 different brain areas were injured in patients in PVS compared with 4.6 areas in patients who had NPVS. Patients in PVS revealed a significantly higher frequency of corpus callosum, corona radiata, and dorsolateral brainstem injuries than did patients who recovered. Logistic regression analysis showed that corpus callosum and dorsolateral brainstem injuries were predictive of non-recovery. The adjusted odds ratios for non-recovery of patients with a corpus callosum lesion and dorsolateral brainstem injury were 213.8 (95% CI 14.2-3213.3), and 6.9 (11-42.9), respectively. In contrast, clinical characteristics, such as initial score on the Glasgow Coma Scale, age, and pupillary abnormalities failed to predict recovery. INTERPRETATION: Cerebral MRI findings in the subacute stage after head injury can predict the outcome of the post-traumatic VS. Corpus callosum and dorsolateral brainstem lesions are highly significant in predicting non-recovery.
A hospice/palliative medicine consultation team was formed in July 1993 in a U.S. teaching hospital to provide patient care and education. The team consists of an attending physician, nurse, fellow, and any residents or medical students rotating on the service. More than 500 consultations are received each year. Beginning in January 1995,108 consecutive referrals to the service were assessed using a standard form completed by the nurse. The average age was 62 years. The gender of patients was 58% male and 42% female. At the time of consultation 87% were hospitalized on general medical services (including hematology/oncology), 4% were on surgical services, 3% on the neurology service, and 6% were in an intensive care unit. Cancer was the primary diagnosis in 52%, AIDS in 24%, with the rest being distributed among cardiac, renal, pulmonary, neurologic, and other diseases. The most prominent physical symptoms were 48% weakness/malaise, 44% pain, 28% dyspnea, and 23% agitation/confusion. The average length of time patients were followed was 2 days (range 1-10). We conclude that a hospice/palliative medicine consultation service sees a broad range of patients and problems and is a rich resource for teaching hospice and palliative medicine.
OBJECT: In this retrospective study, the authors analyzed the frequency, anatomical distribution, and appearance of traumatic brain lesions in 42 patients in a posttraumatic persistent vegetative state. METHODS: Cerebral magnetic resonance (MR) imaging was used to detect the number of lesions, which ranged from as few as five to as many as 19, with a mean of 11 lesions. In all 42 cases there was evidence on MR imaging of diffuse axonal injury, and injury to the corpus callosum was detected in all patients. The second most common area of diffuse axonal injury involved the dorsolateral aspect of the rostral brainstem (74% of patients). In addition, 65% of these patients exhibited white matter injury in the corona radiata and the frontal and temporal lobes. Lesions to the basal ganglia or thalamus were seen in 52% and 40% of patients, respectively. Magnetic resonance imaging showed some evidence of cortical contusion in 48% of patients in this study; the frontal and temporal lobes were most frequently involved. Injury to the parahippocampal gyrus was detected in 45% of patients; in this subgroup there was an 80% incidence of contralateral peduncular lesions in the midbrain. The most common pattern of injury (74% in this series) was the combination of focal lesions of the corpus callosum and the dorsolateral brainstem. In patients with no evidence of diffuse axonal injury in the upper brainstem (26% in this series), callosal lesions were most often associated with basal ganglia lesions. Lesions of the corona radiata and lobar white matter were equally distributed in patients with or without dorsolateral brainstem injury. Moreover, cortical contusions and thalamic, parahippocampal, and cerebral peduncular lesions were also similarly distributed in both groups. CONCLUSIONS: The data indicate that diffuse axonal injury may be the major form of primary brain damage in the posttraumatic persistent vegetative state. In addition, the authors demonstrated in this study that MR imaging, in conjunction with a precise clinical correlation, may provide useful supportive information for the accurate diagnosis of a persistent vegetative state after traumatic brain injury.
Genuine saponins of Solidago virgaurea L., Heteropappus altaicus (Willd.) Novopokr., Heteropappus biennis (Ldb.) Tamamsch. and Helianthus annuus L. (Asteraceae) as well as related carbohydrate modified glycosides of polygalacic acid and echinocystic acid and some commercial available triterpenoid saponins were investigated in view of their immunomodulating and antitumoral effects. Mitogeneic effects on murine spleen and thymus cells, as well on human mononuclear cells in vitro could be demonstrated. The activity of murine bone marrow macrophages was stimulated in a chemoluminescence assay, and further an induction of cytotoxic macrophages and a TNF alpha release from murine macrophages was observed. The mitogeneic and TNF alpha releasing virgaureasaponin E (1) showed in vivo antitumoral effects in the allogeneic sarcoma 180 tumor model and in the syngeneic DBA/2-MC.SC-1 fibrosarcoma tumor model. In mice, treated with 1, phagocytosis of bone marrow cells and proliferation of spleen and bone marrow cells were stimulated in an ex vivo assay whereby the TNF alpha concentration in blood considerably increased compared to the control group.
In the medfly Ceratitis capitata, the Y chromosome is responsible for determining the male sex. We have mapped the region containing the relevant factor through the analysis of Y-autosome translocations using fluorescence in situ hybridization with two different probes. One probe, the clone pY114, contains repetitive, Y-specific DNA sequences from C. capitata, while the second clone, pDh2-H8, consists of ribosomal DNA sequences from Drosophila hydei. Clone pY114 labeled most of the long arm and pDh2-H8 hybridizes to the short arm and the centromeric region of the long arm. In 12 of the analyzed 19 Y-autosome translocation strains, adjacent-1 segregation products survive to the late pupal or even adult stage and can, therefore, be sexed. This was correlated with the length of the Y fragment still present in these aberrant individuals and allowed us to map the male-determining factor to a region of the long arm representing approximately 15% of the entire Y chromosome. No additional factors, affecting for example fertility, were detected outside the male-determining region.
Effects of gamma radiation on the egg and larval stages of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), were examined. Eggs and larvae were exposed at different ages to a series of gamma radiation doses ranging from 5 to 1,280 Gy. Eggs in the 1st half of their development (1 and 24 h) were very sensitive to irradiation treatment (20 Gy prevented egg hatch). However, mature eggs (48 h old) were much more tolerant. When mature eggs were irradiated, a dose of 640 Gy prevented egg hatch. Pupariation of eggs treated at 1 and 24 h was significantly affected at a dose of 20 Gy; adult emergence of eggs at 1, 14, and 48 h was prevented at this dose. The larval stage was significantly more resistant to radiation than the egg stage. Survival to the pupal stage increased with increasing age of larvae, and decreased with increasing dose. The minimum dose required to prevent pupariation ranged from over 160 Gy for the 1st instar to > 640 Gy for mature 3rd instars. In contrast, doses required to prevent adult emergence from irradiated larvae were relatively low and ranged from 10-20 to 20-40 Gy depending on the age of the insects when irradiated. Tests in which > 100,000 mature larvae were treated in air with a dose of 40 Gy resulted in no adult emergence. Similar results were obtained when 3rd instars were irradiated inside natural host fruits in a small scale laboratory experiment.
Genuine saponins from Solidago virgaurea L., Heteropappus altaicus (Willd.) Novopokr., H. biennis (Ldb.) Tamamsch., and Helianthus annuus L. (Asteraceae) as well as related carbohydrate modified glycosides of polygalacic acid and echinocystic acid were investigated in view of their structure related cytotoxicity in the YAC-1- and in the P-815-tumor cell model. The cytotoxic activities are influenced by both, the O-glycosylation pattern at carbon atom 3 and 28 of the sapogenin. The IC50-values of bisdesmosides of polygalacic acid are lower than those of the corresponding prosapogenins. The acylglycosidic carbohydrate sequence 1-fucose-2 <-- 1-rhamnose-4 <-- 1-xylose-3 <-- 1-rhamnose of these bisdesmosides showed the highest cytotoxic effect. One etherglycosidic linked glucose unit at C-3 of the aglycone is essential, a difference in activity to the disaccharide laminaribiose at the same position cannot be observed. In the case of echinocystic acid glycosides the acylglycosidic carbohydrate sequence 1-arabinose-2 <-- 1-rhamnose-4 <-- 1-glucose seems to influence the rate of the cytotoxic effects. By comparing the concentration of the saponins with the complete hemolysis time it is possible to determine the hemolytical index in a very short time. Cytotoxicity against tumor cells correlated with the basic structure of the saponins are in accordance with the hemolytical effect. Sugar moieties play an important role for the hemolytical index.
Sulfation of the natural polysaccharide curdlan results in anticoagulantly active beta-1,3-glucan sulfates whose activity depends on various structural parameters. In this study the anticoagulant and antithrombotic effects of one of these beta-1,3-glucan sulfates (GS) were compared with those of a porcine mucosal heparin. GS produced a concentration dependent anticoagulant effect in all the global coagulation assays with the exception of the anti-Xa assay. The best activity was found in the APTT and the thrombin time assays indicating that protease generation and the direct inhibition of thrombin may be sites of actions of this agent. Whereas the anticoagulant activity of GS was approximately 5 fold lower compared to heparin, a 32 fold higher concentration (ED50 = 550 micrograms/kg) was needed for an antithrombotic effect similar to heparin (ED50 = 17.2 micrograms/kg) in a rabbit model of stasis thrombosis. In contrast to this, when a rat model of clamping induced jugular vein occlusion was used to produce vascular obstruction, GS produced similar antithrombotic actions to heparin. At a 250 micrograms/kg dosage, both agents doubled the number of clampings required for complete vascular obstruction. Since the mechanical injury to the blood vessel is the primary determinant of the thrombogenic response, GS may inhibit some of the pathophysiologic mechanisms responsible for the occlusion of the blood vessel. The current study also points to the fact that the global anticoagulant effects may not reflect the antithrombotic potential of newer sulfated carbohydrate derived drugs.
Heparin has been the drug of choice in clinical pre-surgical and post-surgical prophylaxis of thrombotic events. However, because of its side-effects, such as bleeding and other disadvantages (i.e. chemical inhomogeneity and variability of its physiological activities), alternatives to heparin are an important field of research. A necessary procedure in the development of new drugs is the evaluation of structure-activity relationships. Genuine neutral polysaccharides were chemically modified and examined for their anticoagulant activities. The linear beta-1,3-glucan curdlan, an easily available bacterial polysaccharide, served as the basic polymer. It could be established that the anticoagulant activity was dependent on the degree of sulfation and the molecular weight. For heparin, the sulfation pattern, i.e. the actual location of the sulfate groups along the heparin chain, was of importance in addition to the degree of sulfation. Therefore, we investigated whether there was also a relationship between the substitution pattern of the curdlan sulfates and their anticoagulant activity. For determination of the substitution pattern of the sulfated polysaccharides, a method was developed that is based on synthesis of the partially alkylated alditol acetates of the polymer and examination of these derivatives using combined gas chromatography-mass spectrometry. In addition to the analytical data, the structure-activity relationship of anticoagulative curdlan sulfates is presented.
We have evaluated a series of laminarin sulphates with different degrees of sulphation (0.3-2.3) as antagonists of basic fibroblast growth factor (bFGF) and as inhibitors of the bFGF-dependent endothelial cell line FBHE. Inhibition of binding of bFGF by the laminarin sulphates increased with increasing degree of sulphation. Binding of bFGF to low affinity sites on BHK cells was inhibited more strongly than binding to high affinity sites. IC50 values for inhibition of binding to low and high affinity sites by the most highly sulphated laminarin sulphate (LAM S5; degree of sulphation 2.31) were 12 +/- 8 micrograms/ml and 69 +/- 66 micrograms/ml, respectively. LAM S5 dissociated bFGF from low affinity sites on BHK cells but not from high affinity sites. LAM S5 increased the electrophoretic mobility of bFGF indicating that LAM S5 binds directly to bFGF. LAM S5 reduced uptake of bFGF by FBHE cells by 67%. Increasing the degree of sulphation of laminarin sulphates increased the inhibition of bFGF-stimulated DNA synthesis of the endothelial cell line FBHE (IC50 for LAM S5 approx. 1 microgram/ml). There was no inhibition of DNA synthesis of FBHE cells by LAM S5 in the presence of 1 microgram/ml bFGF indicating that bFGF antagonism is involved in the anti-proliferative activity of this compound. LAM S5 may be of value against diseases associated with bFGF-dependent cell proliferation.
HAT is the most frequent drug induced immune-thrombocytopenia. We recently identified multimolecular PF4/heparin complexes as the major antigen. In order to evaluate the structural requirements for formation of the antigenic complex, we chemically synthesized 13 glucan sulfates and used 5 heparin fractions (2.4-4.8 kD) and a synthesized pentasaccharide, representing the antithrombin III binding sequence of heparin, for further characterize the HAT antigen. In the presence of glucan sulfates and heparin, HAT antibodies caused platelet activation typically at low but not at high concentrations, as measured by 14C-5HT release. The concentration range giving the activation pattern depended on the degree of sulfation (DS) and molecular weight (MW) of the glucan sulfates but not on the type of glycosidic linkage of a polysaccharide. With linear glucan sulfates with a chain length of 35 monosaccharides, the critical DS to form the HAT antigen ranged between 0.60 and 1.20. Glycosidic branched glucan sulfates were able to form the HAT antigen at a lower DS and a lower MW than linear glucan sulfates. Platelet activation by HAT-antibodies in the presence of linear curdlan sulfate fractions was dependent on their MW. At a low concentration (0.01 microM) medium-size fractions (60 kD) caused platelet activation but neither small (12 kD) nor large fractions ( > 150 kD) did. At higher concentrations (2 microM) the opposite reaction pattern was observed. In the case of heparin, the optimal chain length for forming the HAT antigen is a hexadecasaccharide (4.8 kD). Antigen generation decreased with larger and smaller fractions.(ABSTRACT TRUNCATED AT 250 WORDS)
Elements related to the Tc1-like Minos mobile element have been cloned from Drosophila hydei and sequenced. Southern blot and sequence analyses show that (i) the elements are actively transposing in the Drosophila hydei germ line, (ii) they are characterized by a striking degree of sequence and size homogeneity, and (iii) like Tc1, they insert at a TA dinucleotide that is probably duplicated during the process. The nucleotide sequences of two elements, Minos-2 and Minos-3, differ at only one position from each other and contain two nonoverlapping open reading frames that are separated by a putative 60-nucleotide intron. The amino-terminal part of the Minos putative transposase shows sequence similarity to the paired DNA-binding domain. Forced transcription of a modified Minos element that was introduced into the Drosophila melanogaster germ line by P element-mediated transformation resulted in the production of accurately spliced polyadenylylated RNA molecules. It is proposed that Minos-2 and/or Minos-3 may encode an active transposase containing an amino-terminal DNA-binding domain that is distantly related to the paired DNA-binding domain.
A cytogenetic map of chromosome 5 from the Mediterranean fruit fly, Ceratitis capitata, was constructed. Six mutations were located by translocation, transposition or deletion mapping. This knowledge allowed alignment and orientation of the existing linkage map with the polytene chromosomes. In addition, mapping of mutations used as selectable markers in genetic sex-separation strains is an essential prerequisite for the improvement of genetic stability during mass-rearing.
1. To evaluate the sulfation pattern of anticoagulant active curdlan sulfates, a methylation method, based on the synthesis of alkylated alditol acetates, followed by GLC-MS examination, was developed. 2. By the specific cleavage of the sulfate esters, using solvolysis and the substitution of these liberated OH groups with ethyl iodide, a third kind of substitution was introduced in the alkylated alditol acetates, specifically replacing the former sulfate esters. 3. The primary OH group in position 6 had more than the 10-fold accessibility to sulfation, in comparison to the secondary OH groups in positions 2 and 4. 4. Products with a low DS were fairly homogenously substituted, having unsubstituted or selectively C6-sulfated glucose units. Increasing DS was associated with a loss of homogeneity as well as selectivity of the C6 sulfation. 5. Sulfation of C6-protected curdlan resulted in products with a higher content of sulfate groups in positions 2 and 4, and consequently a uniform charge distribution around the glucose monomer. 6. Besides the dependence on the DS and the MW, also the sulfation pattern influenced the anticoagulant activity. The higher the portion of the secondary linked sulfate esters, the higher the anticoagulant activity. The C6-protected curdlan sulfates had activities normally corresponding to higher DS and MW.
Senna consists of the dried leaflets or fruits of Cassia senna (C. acutifolia) known in commerce as Alexandrian senna and of Cassia angustifolia commonly known as Tinnevelly senna. The senna plants are small shrubs of Leguminosae cultivated either in Somalia, the Arabian peninsula and near the Nile river. Tinnevelly senna is obtained from cultivated plants mainly in South India and Pakistan. Owing to the careful way in which the plant is harvested, the leaflets of the drug are usually little broken. Damaged leaves and lower quality products are often used for making galenicals. The senna pods (fruits) are collected during the same period as the leaves, then dried and separated into various qualities. The active principle of Senna was first isolated and characterized by Stoll in 1941. The first two glycosides were identified and attributed to the anthraquinone family. These were found to be dimeric products of aloe emodin and/or rhein which were named sennoside A and sennoside B. They both hydrolyze to give the aglycones sennidin A and B and two molecules of glucose. Later work confirmed these findings and further demonstrated the presence of sennosides C and D. Small quantities of monomeric glycosides and free anthraquinones seem to be present as well. The active constituents of the pods are similar to those of the leaves but present in larger quantities. Two naphthalene glycosides isolated from senna leaves and pods are 6-hydroxymusicin glucoside and tinnevellin glucoside. Both compounds can be utilized to distinguish between the Alexandrian senna and the India senna, since tinnevellin glucoside is only found in the latter and the first only in the C. senna.(ABSTRACT TRUNCATED AT 250 WORDS)