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S Cramer

Publications and source records attributed to S Cramer.

18 recordsLinked to original sources
PubMed2005

SNAT expression in rat placenta.

Amino acid transport System A (SysA) activity is present within the rodent and human placentas. Inhibition of this transport system is associated with fetal growth retardation. Several cDNAs encoding SysA transport proteins have been discovered, and their presence documented within the human placenta. We have demonstrated the presence of mRNA encoding three of these transporters, SNAT1, 2, and 4 within the rat placenta over the final third of gestation. Abundance of these mRNA species increases from day 14 to day 20 of gestation. Immunohistochemistry demonstrates the presence of SNAT1 and 2 within the placental labyrinth at both days 14 and 20. Transport proteins are also present within marginal giant cells and, for SNAT1, within fetal endothelium. In conclusion, several proteins capable of SysA transport activity are present within the rodent placenta. mRNA expression increases over the final third of gestation, coincident with the period of greatest need for fetal amino acid delivery.

Amino Acid Transport System A↗
PubMed1998

Differences in kindling development in seven outbred and inbred rat strains.

The kindling phenomenon, i.e., the progressive development of focal and secondarily generalized seizures upon repeated electrical stimulation of a limbic brain region, occurs in various species, but with marked differences in kindling rate between species and also within the same species. In rats, differences in kindling rates have been reported within the same strain and between different strains, and both genetic and environmental influences are thought to be involved in this variability. In most studies on kindling in rats, outbred strains such as Sprague-Dawley have been used. In the present study, we compared rates of amygdala kindling development in two outbred (Sprague-Dawley, Wistar) and five inbred (Lewis, Fischer 344, ACI, Wistar-Kyoto, Brown Norway) rat strains, including several strains which have not been kindled before. We were particularly interested which parts of the stepwise progression of kindling differ among these strains. Furthermore, the sensitivity of the basolateral amygdala to electrical stimulation was determined before and after kindling. Once daily electrical stimulation of the basolateral amygdala resulted in marked interstrain differences in kindling rates, with Sprague-Dawley and Brown-Norway rats exhibiting the lowest number of stimulations to reach fully kindled (stage 5) seizures, and Lewis rats showing the highest number of the 7 strains. In contrast to the significant differences in number of stimulations to reach the fully kindled state, total (cumulative) afterdischarge duration (ADD) to reach stage 5 did not significantly differ among strains, substantiating that cumulative AD is the principal factor in the acquisition of kindled seizures. Marked differences in ADD of a stage 5 seizure were obtained between strains, with strains kindling rapidly exhibiting longer ADD than strains kindling slowly. Postkindling afterdischarge threshold (ADT) varied significantly among strains, but only 3 of the 7 strains showed a decrease of ADT compared to prekindling values. When the stepwise progression of kindling was evaluated, pronounced interstrain differences were determined in the time spent in the initial phase of kindling, i.e., stage 1 seizures, both in terms of stimulations and cumulative ADD, indicating that variations in kindling rates were predominantly due to the time needed to progress from stage 1 to subsequent stages of the kindling process. The data seem to indicate that inbred rat strains offer an interesting resource for dissecting the underlying genetic basis for phenotypic differences in epileptogenesis as induced by kindling, although the high variability of kindling rates seen within some inbred strains weakens this possibility.

Amygdala↗
PubMed1998

Resistance to Trypanosoma cruzi infection in mice does not necessarily correlate with production of interferon-gamma in vivo.

Interferon-gamma (IFN-gamma) is the most important mediator of inhibition of intracellular replication of Trypanosoma cruzi in vitro and has a protective effect against this parasite if administered in vivo. Here we have analyzed the importance of IFN-gamma for resistance against a lethal infection with T. cruzi in a mouse model system. Resistant B6D2 mice survived the infection with a virulent strain of T. cruzi, whereas susceptible BALB/c mice died within 3 weeks. Both strains produced large amounts of IFN-gamma after infection. Surprisingly, susceptible mice had higher serum concentrations of IFN-gamma and showed, using in situ hybridization a stronger increase in IFN-gamma mRNA-producing cells in their spleens than resistant mice. Moreover, this pattern was also found when immune spleen cells were stimulated with parasite antigens in vitro. However, a marked difference between these mice was found in the production of IL-4, which was much higher in susceptible mice in vivo and in vitro. No difference was found for IL-10. These data show that, at least in the mouse strain/parasite combination used, production of IFN-gamma is not the decisive factor determining resistance or susceptibility to T. cruzi. Rather, it is possible that the balance between protective (e.g., IFN-gamma) and exacerbative cytokines (e.g., IL-4) may decide over disease control or progression.

Animals↗
PubMed1998

Limbic epileptogenesis alters the anticonvulsant efficacy of phenytoin in Sprague-Dawley rats.

Studies on the anticonvulsant efficacy of the major antiepileptic drug phenytoin in kindled rats have often reported inconsistent effects. It has been proposed that technical and genetic factors or poor and variable absorption of phenytoin after i.p. or oral administration may be involved in the lack of consistent anticonvulsant activity of phenytoin in this model of temporal lobe epilepsy. We examined if kindling itself changes the anticonvulsant efficacy of phenytoin by testing this drug before and after amygdala kindling in male and female Sprague-Dawley rats. To exclude the possible bias of poor and variable absorption, blood was sampled in all experiments for drug analysis in plasma. The threshold for induction of focal seizures (afterdischarge threshold; ADT) was used for determining phenytoin's anticonvulsant activity. Before kindling, phenytoin, 75 mg/kg i.p., markedly increased ADT in both genders, although the effect was more pronounced in males. Following kindling, the anticonvulsant activity obtained with phenytoin, 75 mg/kg, before kindling was totally lost, and female rats even exhibited a proconvulsant effect upon administration of this dose, indicating that kindling had dramatically altered the anticonvulsant efficacy of phenytoin. Plasma levels of phenytoin were comparable before and after kindling, and were within or near to the 'therapeutic range' known from epileptic patients. When the dose of phenytoin was reduced to 50 or 25 mg/kg i.p., significant anticonvulsant effects on ADT were obtained. When phenytoin, 50 mg/kg, was administered i.p. or i.v. in the same group of fully kindled rats, both anticonvulsant activity and plasma drug levels were comparable with both routes, indicating that the i.p. route is suited for such studies. The data indicate that kindling alters the dose-response of phenytoin in that a high anticonvulsant dose becomes ineffective or proconvulsant after kindling, possibly by an increased sensitivity of the kindled brain to proconvulsant effects of phenytoin which normally only occur at much higher doses. If similar alterations evolve in humans during development of chronic epilepsy, this may be involved in the mechanisms leading to intractability of temporal lobe epilepsy.

Amygdala↗
PubMed1998

Characterization of phenytoin-resistant kindled rats, a new model of drug-resistant partial epilepsy: comparison of inbred strains.

PURPOSE: Previous work from our laboratory showed that amygdala-kindled Wistar outbred rats can be selected according to the increase of afterdischarge threshold (ADT) after phenytoin application. Animals that consistently do not respond to phenytoin (PHT) with an ADT increase (non-responders) are the first animal model of pharmacoresistant complex partial seizures. In this study, we determined the ability to respond to PHT in male kindled rats of different inbred strains. METHODS: The experiments were performed in fully kindled rats of five different inbred strains, Wistar-Kyoto, Lewis, Fischer 344, ACI, and Brown Norway. The response type of each rat was revealed by four consecutive PHT applications (75 mg/kg, i.p.) in fully kindled rats. RESULTS: PHT application resulted in plasma concentrations ranging from some 16 microg/ml in Lewis rats to 35 microg/ml in Fischer 344 rats, and in slight ataxia, most strongly in Fischer 344 rats. The rats of each strain did not show a homogeneous response to PHT. A significant increase of ADT was found after 86-97% of applications in Lewis, Wistar-Kyoto, and Fischer 344 rats. In contrast, Brown Norway rats responded in only 34% of experiments. This led to a considerable number of responders (i.e., consistent ADT increase by >20%) in Fischer 344, Wistar-Kyoto, and Lewis rats. The only strain revealing nonresponders (i.e., consistent lack of ADT increase by >20% with PHT treatment) was Brown Norway. CONCLUSIONS: Inbred strains, although genetically more homogenous than outbred strains, differ in their response to PHT. Brown Norway rats can offer advantages for further detailed investigation of the resistance to PHT in the kindling model of complex partial seizures.

Animals↗
PubMed1998

Selection of phenytoin responders and nonresponders in male and female amygdala-kindled Sprague-Dawley rats.

PURPOSE: We recently described that, by repeated testing of the anticonvulsant phenytoin (PHT), it is possible to select responders and nonresponders from large populations of amygdala-kindled Wistar rats. Whereas responders show marked and reproducible increases of focal seizure threshold (afterdischarge threshold: ADT) on repeated testing of PHT, 75 mg/kg i.p., nonresponders do not show any significant ADT increase after this dose, thus allowing use of these subgroups in the search for mechanisms of pharmacoresistance in temporal lobe epilepsy. In this study, we examined whether PHT responders and nonresponders can also be selected from large groups of kindled rats of the Sprague-Dawley strain. METHODS: Male and female Sprague-Dawley rats were amygdala kindled, followed by once weekly i.p. testing of PHT. RESULTS: In contrast to recent experiments in Wistar rats, 75 mg/kg PHT did not induce significant ADT increases in Sprague-Dawley rats, indicating strain differences in response to this drug after kindling. When the dose was lowered to 50 or 25 mg/kg, significant and reproducible ADT increases were obtained in Sprague-Dawley rats of both genders. Therefore these doses were used for selection of responders and nonresponders in a total of 42 rats. Almost 50% of the rats were PHT responders, whereas no rat was a nonresponder when tested in up to six subsequent drug trials. Many rats were variable responders (i.e., showed ADT increases in some but not all trials), which was not due to low or variable drug absorption after i.p. injection. CONCLUSIONS: The data indicate that, in contrast to Wistar rats, Sprague-Dawley rats are not suited for selection of PHT nonresponders, but rather are quite responsive to this drug. A further difference to the Wistar strain is the truncated dose-response with loss of anticonvulsant efficacy at 75 mg/kg in kindled Sprague-Dawley rats, which may, at least in part, explain the inconsistent results reported on the anticonvulsant efficacy of PHT in this strain in the literature. The lack of anticonvulsant activity after administration of 75 mg/kg may be a result of kindling, because administration of this dose before kindling causes a significant ADT increase in this strain. This kindling-induced alteration of the anticonvulsant activity of PHT is a phenomenon that contrasts Sprague-Dawley with Wistar rats and deserves further investigation.

Amygdala↗
PubMed1997

Phenytoin's effect on the spread of seizure activity in the amygdala kindling model.

Phenytoin is a major antiepileptic drug for treatment of limbic seizures. The effect of phenytoin on the generation and spread of seizure activity was studied in a rat model of this type of seizures. Sprague-Dawley and Wistar rats were implanted with a stimulation and recording electrode in the basolateral amygdala. Naive Sprague-Dawley rats showed an increase in current intensity necessary for eliciting afterdischarges (afterdischarge threshold) of about 200% after administration of phenytoin (75 mg/kg i.p.), while seizure severity at threshold was increased compared to controls. Afterdischarge and seizure durations were significantly prolonged under phenytoin. This result suggests that phenytoin can exert a potent anticonvulsant effect on the generation of focal seizure activity, but it does not suppress or may even increase ongoing afterdischarge activity once it occurs. Following amygdala kindling in Wistar rats, administration of phenytoin again resulted in an increase in the afterdischarge threshold. However, all rats still showed generalized seizures, and epileptic afterdischarges could be recorded in various limbic brain regions at threshold current. This result suggests that phenytoin can increase the threshold for generation of epileptic discharges in kindled rats, but is not able to prevent the development of generalized seizure activity and the spread of afterdischarges within the limbic system when focal activity is initiated. We conclude that phenytoin is able to suppress focal seizure activity in the amygdala kindling model of the rat. However, it does not prevent the spread of seizure activity originating in the limbic system. Therefore, a decrease in focal seizure susceptibility seems to be the primary target for phenytoin's anticonvulsant action.

Animals↗
PubMed1997

Trypanosoma cruzi induces strong IL-12 and IL-18 gene expression in vivo: correlation with interferon-gamma (IFN-gamma) production.

IFN-gamma, produced after infection with Trypanosoma cruzi, has been shown to be crucial in the determination of resistance or susceptibility. We have performed a detailed study on the expression of IFN-gamma and of the IFN-gamma-inducing cytokines IL-12 and IFN-gamma-inducing factor (IGIF)/IL-18 with regard to time course and tissue localization. IFN-gamma was present in high amounts in the serum and in the supernatants of unseparated spleen cells and isolated CD4+ and CD8+ T cells from the spleens of infected mice which were stimulated ex vivo with T. cruzi. Using the in situ hybridization technique we demonstrate that IL-12 p40 messages were expressed in the spleen and increased during infection, correlating with the expression of IFN-gamma transcripts. Furthermore, we show for the first time that the mRNA for the cytokine IL-18 was induced by a parasitic infection and that this expression increased during infection with T. cruzi. Interestingly, the message for IL-18 was produced earlier during infection and already had declined until day 38, when IFN-gamma and IL-12 p40 transcripts were optimally expressed. Surprisingly, the changes in IL-12 and IL-18 mRNA production were clearly seen only by in situ hybridization, but less clearly by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). This is possibly due to the extensive activation and proliferation of spleen cells observed during infection leading to a dilution of these specific mRNAs.

Animals↗
PubMed1991

[Long-term results of elective percutaneous transluminal coronary angioplasty. A clinico-angiography study of 289 consecutive patients].

289 consecutive patients (255 male, 34 female, 50 +/- 6 years) had an elective single-vessel-PTCA between October 1978 and March 1983. A clinical long-term follow-up was obtained after 4.7 (3-10) years. The PTCA success-rate was 73% with a non steerable balloon catheter being used in 95% of the cases. For 271/289 patients with follow-up (94%), the 56-month-survival rate was 96%, the incidence of non-fatal myocardial infarctions 11%, and the need for a second intervention (PTCA and/or bypass surgery) was 39%. The most favorable long-term outcome was observed in patients without need of a second intervention (97% survival, 7% non-fatal myocardial infarction, 83% without cardiac complaints during everyday life), and in patients with elective bypass surgery after an unsuccessful PTCA (100% survival, 5% myocardial infarction). 32/138 (23%) of patients without a second intervention during follow-up underwent an angiographic control after an average of 4.7 years. In comparison with the first follow-up angiogram 6 months after PTCA, the mean residual stenosis at the PTCA-site showed a slight decrease. It is concluded that PTCA offers good clinical and angio-graphic long-term results in single-vessel disease, with an excellent prognosis of patients without need for a second intervention.

Angioplasty, Balloon, Coronary↗
PubMed1990

The importance of renal ammonia metabolism to whole body acid-base balance: a reanalysis of the pathophysiology of renal tubular acidosis.

Traditionally, the renal collecting duct has been assigned the dual role of (1) secreting protons derived from dietary metabolism to form luminal NH4+ and titratable acid and (2) generating new HCO3-. This view has recently been challenged. According to current concepts, whole body proton balance is maintained predominantly by the lungs which excrete protons derived from dietary metabolism as the acid anhydride CO2. In the process of excreting CO2, HCO3- is also lost from the body. It is the function of the kidney to generate new HCO3- to replenish this loss. The major site of new HCO3- generation is the proximal tubule rather than the collecting duct. New HCO3- is generated predominantly via the metabolism of organic anions, i.e. alpha-ketoglutarate, citrate, lactate, fatty acids. In the process of generating alpha-ketoglutarate from glutamine, NH4+ is formed. Under normal acid-base conditions, 50% of the NH4+ produced is excreted in the urine, and the remaining 50% is delivered to the renal veins. NH4+ delivered to the renal veins consumes HCO3- during ureagenesis. In the discussion which follows, these new concepts are reviewed and applied to an analysis of the pathophysiology of renal tubular acidosis.

Acid-Base Equilibrium↗
PubMed1989

Differential proliferative response to linoleate in cultures of epithelial cells from normal human breast and fibroadenomas.

Human breast epithelial cells isolated from normal breast tissues of premenopausal women demonstrated direct evidence of a proliferative effect by linoleate (18:2 omega 6) or prostaglandin E2 (PGE2) in the presence of insulin and epidermal growth factor in serum-free cultures within a collagen gel matrix. Neither epidermal growth factor nor 18:2 omega 6 by itself was capable of stimulating growth but together they stimulated proliferation synergistically. Epithelial cells isolated from fibroadenomas on the other hand failed to exhibit any growth stimulation due to 18:2 omega 6 or PGE2. The linoleate-stimulated growth in normal breast epithelial cells was inhibited by indomethacin, a cyclooxygenase inhibitor, which however could be reversed by PGE2. The proliferative response of normal breast epithelial cells to 18:2 omega 6 was accompanied by a greater conversion of [14C]18:2 omega 6 to arachidonic acid and [14C]20:4 omega 6 to prostaglandins than that seen in epithelial cells from fibroadenomas. The turnover of [14C]18:2 omega 6 in the phospholipids of normal cells was higher than in fibroadenomas indicating a possible role of phospholipids in mediating the 18:2 omega 6 effect in normal cells. Both normal and fibroadenoma cells can proliferate in response to cholera toxin and glucocorticoids when supplemented to the insulin- and epidermal growth factor-containing medium. From the results it appears that, unlike normal cells, fibroadenoma cells may have a specific defect in the PGE2-responsive cyclic AMP-generating mechanism whereas cholera toxin-induced mechanism is operative in both types of cells.

Adenofibroma↗
PubMed1981

Serous ovarian neoplastic amylase (SONA): a potentially useful marker for serous ovarian tumors.

A series of cystic ovarian tumors was studied with regard to amylase activity in the cyst fluid. Large amounts of amylase activity were present only in those patients with endosalpingeal-type lining epithelium (serous ovarian neoplasms). The amylase activity from two such patients was further characterized using G75 Sephadex chromatography, DEAE Sephadex chromatography, agarose gel chromatography, isoelectric focusing, and heat inactivation studies. Serous ovarian neoplastic amylase (SONA) exhibited properties different from amylases of pancreatic and salivary gland origin. Serous ovarian neoplastic amylase (SONA) may be a pancreatic and salivary gland origin. Serous ovarian neoplastic amylase (SONA) may be a useful biochemical marker in diagnosing and managing patients with serous ovarian neoplasms.

Amylases↗
PubMed1980

Invertible DNA determines host specificity of bacteriophage mu.

The function of the invertible G region of bacteriophage Mu is apparently to confer different host specificities on Mu. Two products of genes S and U, situated in the G region are not needed for the infectivity of Mu G(-) particles. In the Mu G(-) phage the S gene product and the 21-K polypeptide, presumably the product of gene U, are missing. Instead, two other polypeptides with different molecular weights are observed.

Bacteriophage mu↗
PubMed1977

Massive hemorrhage from perforated thyroid complicating tracheostomy. Report of two cases.

Two cases of unusual hemorrhagic complication of tracheostomy involved perforation of the thyroid gland as the cause of hemorrhagic episodes. In one case, massive hemorrhage complicated the postoperative course of a 62-year-old man with dissecting aortic aneurysm. In the other, fatal hemorrhage occurred after tracheostomy through the thyroid gland in a 6-month-old boy. A major branch of the thyroid artery was ruptured adjacent to the tracheostomy wound. This is the sixth reported case of fatal hemorrhage from perforation of thyroid artery after tracheostomy, to our knowledge.

Arteries↗
PubMed1976

Resonance enhanced coherent anti-Stokes Raman scattering.

Resonance enhancement of coherent anti-Stokes Raman scattering due to the proximity of the laser frequencies to an electronic transition has been demonstrated for dilute solutions of diphenyloctatetrane in benzene. The Raman contribution to the third order susceptibility is shown to be complex near an electronic resonance and the resulting features of the coherent anti-Stokes Raman scattering spectra are discussed in detail. This work represents one step in the demonstration that the high signal to noise ratio, fluorescence rejection, and low average power levels of the coherent anti-Stokes Raman scattering experiment can be used to advantage in Raman studies of dilute solutions and materials of biological interest.

Benzene Derivatives↗