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Biomedical subjects

C Schultz

Publications and source records attributed to C Schultz.

At least 73 records · Page 4Linked to original sources
PubMed1996

Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of radiation therapy oncology group protocol 88-06.

PURPOSE: This study was a prospective phase I/II trial performed by the Radiation Therapy Oncology Group (RTOG) to test the tolerance and efficacy of preirradiation cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) chemotherapy followed by large-volume, high-dose brain radiation therapy (RT) for patients with primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: Fifty-four (52 assessable) human immunodeficiency virus (HIV)-negative patients with PCNSL were entered on study and received two (n = 20) or three (n = 32) cycles of CHOD (six patients with positive CSF cytology received intrathecal methotrexate in addition to CHOD). Whole-brain RT to 41.4 Gy and tumor boost to 18 Gy (total dose, 59.4 Gy) followed chemotherapy. RESULTS: As of July 1994, with a minimum potential follow-up time of 20 months, 12 of 52 assessable patients remain alive without evidence of progression. The median survival time for the entire group is 16.1 months, with a 2-year survival rate of 42%. By univariate analysis, patient age was found to be a significant prognostic factor with respect to survival (P = .005) in favor of age less than 60 years. Karnofsky performance status (KPS) was of borderline significance (P = .057). Survival for patients treated on RTOG 88-06 was compared with that of patients treated on RTOG 83-15, which tested RT alone. No difference in overall survival was found (P = .53). Grade 4 neutropenia developed in 29 of 51 patients during chemotherapy. There were two deaths during chemotherapy: one as a result of sepsis and one of a pulmonary embolus. The worst toxicity during RT was < or = grade 2 in 50 of 52 patients. CONCLUSION: Preirradiation CHOD chemotherapy does not significantly improve survival over RT alone for patients with PCNSL. Age remains a powerful prognostic factor independent of therapy and must be considered in testing alternative combined approaches.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Peripheral neuroectodermal tumor of the thoracic wall. Experiences with surgical treatment].

The peripheral neuroectodermal tumor (PNET) is seen nowadays as a more specified form of Ewing's Sarcoma with a worse prognosis. We report our experiences of three children (10-14 years old) with PNET of the right thoracic wall, all treated surgically within 1 year. Complete local resection-the main aspect of PNET therapie-of the initially voluminous tumors was not difficult due to chemotherapy and radiotherapy for 5 months prior to surgery.

Adolescent↗
PubMed1995

The critical region in the cytoplasmic domain of human IL-4 receptor for induction of IgE synthesis.

To examine the region critical for differentiation in the human IL-4 receptor (hIL-4R), we transfected the Abelson murine leukemia virus (A-MuLV)-transformed murine pre-B cell line A20 with plasmid DNA encoding the hIL-4R. Transfectants expressed high affinity hIL-4Rs on the cell surface. Treatment with LPS and hIL-4 induced germline C epsilon transcripts in hIL-4R expressing A20 cells. Several hIL-4R mutant plasmids were then transfected into A20 cells and the transfectants were examined for hIL-4R expression and the ability to induce germline C epsilon transcripts upon stimulation with LPS and hIL-4. Although all A20 transfectants tested expressed the high-affinity hIL-4R, A20 transfectants expressing the mutant hIL-4R, which contains only 8 amino acids in the cytoplasmic domain, did not respond to LPS and hIL-4 with germline C epsilon transcripts. In addition, A20 transfectants expressing an internally deleted hIL-4R, in which the deleted region has been identified as the critical region for growth signal transduction in the previous study, failed to induce germline C epsilon transcripts with LPS and hIL-4. These results indicate that the critical region for the differentiation signal in the hIL-4R is identical to that for the growth signal, suggesting that IL-4 may share, at least partly, a common signal pathway for both growth and differentiation.

Animals↗
PubMed1995

Cross-talk between calcium and cAMP-dependent intracellular signaling pathways. Implications for synergistic secretion in T84 colonic epithelial cells and rat pancreatic acinar cells.

Treatment of various cells with combinations of agents that increase either cAMP or cytosolic calcium can lead to synergistic responses. This study examined interactions, or cross-talk, between these two intracellular messengers and its implication for signaling in two secretory cell types, T84 human colonic epithelial cells and rat pancreatic acinar cells. T84 cell chloride secretion was measured in Ussing chambers. Acinar cell activation was monitored as amylase secretion. Cytosolic calcium was assessed via fura-2 microfluorimetry. A cell-permeant analogue of cAMP synergistically enhanced secretory responses to calcium-mobilizing hormones in both cell types, but paradoxically reduced overall calcium mobilization. The reduction in calcium mobilization could be attributed to an inhibition of calcium influx in T84 cells, although a different mechanism likely operates in acinar cells. The effects of the cAMP analogue were reproduced by other agents that increase cAMP. Furthermore, econazole, an inhibitor of calcium influx, potentiated secretory responses to calcium-dependent stimulation in T84 cells without itself inducing secretion. We conclude that there is cross-talk between calcium and cAMP-dependent signaling pathways at the level of second messenger generation in two secretory cell types. This cross-talk appears to regulate the extent of secretory responses.

Amylases↗
PubMed1995

[Laparoscopic interventions in acute and chronic diverticulitis].

UNLABELLED: Since the beginning of 1993 until May 1994 in our hospital 25 patients were operated upon for diverticular disease. 16 patients required a laparoscopic assisted elective one-stage resection. One laparoscopic Hartmann's procedure was performed on account of a free perforation. 4 patients underwent laparoscopic reconstruction of the intestinal continuity after an Hartmann's resection. In 4 cases it was necessary to change to the conventional procedure. TECHNIQUE: the patient is placed in dorso-sacral position (modified lithotomy position) in order to allow transanal colonic access. 4 trocars are necessary. The linear stapler is used to transsect the sigmoid colon and to dissect the entire mesentery. The left lateral trocar incision is enlarged to remove the specimen. The intracorporeal double staple anastomosis is created by a circular stapler. RESULTS: there were two wound infections, one postoperative bleeding and one small anastomotic leak. After the operation we observed all advantages of the laparoscopic procedure in form of less pain, earlier beginning of bowel movements, faster return to full diet and earlier hospital discharge. These positive results combined with the possibility of a standardized procedure encourage us to continue laparoscopic sigmoidectomy.

Acute Disease↗
PubMed1995

Nigral and extranigral pathology in Parkinson's disease.

This article reviews data on the internal organization, neuronal types, and interconnections of limbic and motor components of the human brain, and the specific lesions which a few of them undergo during the course of Parkinson's disease (neuronal loss associated with the development of Lewy bodies and Lewy neurites). The severe involvement of nigral neuromelanin-laden projection cells has received particular attention during the past decades. This lesion interferes with normal function of the striatum and probably contributes to many of the motor dysfunctions characteristically occurring in Parkinson's disease. The similarly severe involvement of several areas and nuclei outside of the substantia nigra has often escaped notice. However, the pathology of Parkinson's disease cannot be completely described unless changes in these extranigral areas are taken into account. Interpretation of the characteristic lesional pattern is facilitated by combining schemata of both the limbic and motor systems. This approach reveals a key role by the amygdala and related structures in extranigral pathology. Severe lesions occur in the central amygdaloid nucleus, in nuclei projecting to the cerebral cortex in a non-specific manner, and in nuclei regulating endocrine and autonomic functions. It is suggested that extranigral lesions contribute to the development of behavioral changes and autonomic dysfunction.

Amygdala↗
PubMed1994

Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4.

Osmoregulation, inhibitory neurotransmission and pH balance depend on chloride ion (Cl-) flux. In intestinal epithelial cells, apical Cl- channels control salt and fluid secretion and are, in turn, regulated by agonists acting through cyclic nucleotides and internal calcium ion concentration ([Ca2+]i). Recently, we found that muscarinic pretreatment prevents [Ca2+]i increases from eliciting Cl- secretion in T84 colonic epithelial cells. By studying concomitant inositol phosphate metabolism, we have now identified D-myo-inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P4), as the inositol phosphate most likely to mediate this uncoupling. A novel, membrane-permeant ester prepared by total synthesis delivers Ins(3,4,5,6)P4 intracellularly and confirms that this emerging messenger does inhibit Cl- flux resulting from thapsigargin- or histamine-induced [Ca2+]i elevations.

Atropine↗
PubMed1994

Impact of point mutations on the structure and thermal stability of ribonuclease T1 in aqueous solution probed by Fourier transform infrared spectroscopy.

We undertook a detailed comparative analysis of the infrared spectra of wild-type ribonuclease T1 and three mutants: two single mutants, Tyr-45-->Trp (Y45W) and Trp-59-->Tyr (W59Y), and a double mutant, Tyr-45-->Trp/Trp-59-->Tyr (Y45W/W59Y). These mutants were selected because they are known to affect the activity of the enzyme. The structural differences were evaluated by using peptide backbone and side-chain "marker" bands as conformation-sensitive monitors. All mutations lead to a decrease of the thermal transition temperature, though the mutation Tyr-45-->Trp affects the Tm to a lesser degree than the replacement of Trp-59 by Tyr, both in the single (W59Y) and in the double (Y45W/W59Y) mutant. Small changes in the protein backbone conformation and in the microenvironment of certain amino acids, induced by the point mutations, could be detected. In particular, we found subtle differences in the hydrogen bonding pattern of the beta-strands in the mutants W59Y and Y45W/W59Y, compared to that in wild-type RNase T1 and in the mutant Y45W. Practically identical spectra in the amide I region were obtained for the double mutant Y45W/W59Y and the single mutant W59Y, demonstrating that it is the change from Trp to Tyr in position 59 (located at the interface between the alpha-helix and a beta-strand) which affects the overall protein conformation. The mutation Tyr to Trp in position 45, on the other hand, has practically no impact on the polypeptide backbone conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspergillus oryzae↗
PubMed1994

Inositol polyanions. Noncarbohydrate inhibitors of L- and P-selectin that block inflammation.

Selectins are cell adhesion molecules known to support the initial attachment of leukocytes to inflamed vascular endothelium through their recognition of carbohydrate ligands such as the tetrasaccharide sialyl Lewisx (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-). In the present study, we describe the inhibition of L- and P-selectin function by inositol polyanions, simple 6-carbon ring structures that have multiple ester-linked phosphate or sulfate groups. In a purified component competition assay, binding of L- and P-selectin-Ig fusion proteins to immobilized bovine serum albumin-sialyl Lewisx neoglycoprotein was inhibited by inositol hexakisphosphate (InsP6, IC50 = 2.1 +/- 1.4 microM and 160 +/- 40 microM), by inositol pentakisphosphate (InsP5, IC50 = 1.4 +/- 0.2 and 260 +/- 40 microM), and by inositol hexakissulfate (InsS6, IC50 = 210 +/- 80 microM and 2.8 +/- 0.9 mM); E-selectin-Ig binding was unaffected. Inositol polyanions diminished the adhesion of LS180 colon carcinoma cells to plates coated with L- and P-selectin-Ig but not with E-selectin-Ig. Inositol polyanions blocked polymorphonuclear leukocyte (PMN) adhesion to COS cells expressing recombinant transmembrane P-selectin but not to those expressing E-selectin. In addition, inositol polyanions diminished PMN adhesion to activated endothelial cells under rotation-induced shear stress, a process known to require L-selectin function. In vivo, the effects of inositol polyanions were studied in two murine models of acute inflammation. Intravenously administered InsP6 (two doses of 40 mumol/kg) inhibited PMN accumulation in thioglycolate-induced inflammation (55 +/- 10% inhibition) and in zymosan-induced inflammation (61 +/- 4% inhibition). InsP5 and InsS6 also inhibited inflammation in these models, although higher doses were required for InsS6. In conclusion, inositol polyanions are noncarbohydrate small molecules that inhibit L- and P-selectin function in vitro and inflammation in vivo.

Animals↗
PubMed1994

Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation.

Several lines of evidence suggest that cyclic GMP might be involved in long-term potentiation (LTP) in the hippocampus. Arachidonic acid, nitric oxide and carbon monoxide, three molecules that have been proposed to act as retrograde messengers in LTP, all activate soluble guanylyl cyclase. We report here that an inhibitor of guanylyl cyclase blocks the induction of LTP in the CA1 region of hippocampal slices. Conversely, cGMP analogues produce long-lasting enhancement of the excitatory postsynaptic potential if they are applied at the same time as weak tetanic stimulation of the presynaptic fibres. The enhancement is spatially restricted, is not blocked by valeric acid (APV), nifedipine, or picrotoxin, and partially occludes LTP. This synaptic enhancement may be mediated by the cGMP-dependent protein kinase (PKG). Inhibitors of PKG block the induction of LTP, and activators of PKG produce activity-dependent long-lasting enhancement. These results suggest that guanylyl cyclase and PKG contribute to LTP, possibly as activity-dependent presynaptic effectors of retrograde messengers.

Action Potentials↗
PubMed1994

Insect calcium channels. Molecular cloning of an alpha 1-subunit from housefly (Musca domestica) muscle.

The complete amino acid sequence of an invertebrate calcium channel alpha 1-subunit from housefly (Musca domestica) larvae (designated Mdl alpha 1) has been deduced by cDNA cloning and sequence analysis. Mdl alpha 1 shares higher percent sequence identity with 1,4-dihydropyridine (DHP)-sensitive L-type than with DHP-insensitive calcium channels. As shown by whole mount in situ hybridization and immunostaining Mdl alpha 1 is predominantly expressed in the larval body wall musculature.

Amino Acid Sequence↗
PubMed1994

Current radiosurgery practice: results of an ASTRO survey. Task Force on Stereotactic Radiosurgery, American Society for Therapeutic Radiology and Oncology.

PURPOSE: Although there is increasing interest in radiosurgery, little quantitative data regarding current patterns of radiosurgery practice are available. We developed a radiosurgery questionnaire to obtain information on radiosurgery practice. METHODS AND MATERIALS: We distributed the questionnaire to the entire membership of the American Society of Therapeutic Radiology and Oncology in early 1993. Responses were obtained from 74 facilities that practice radiosurgery, corresponding to over 6000 treatments carried out since 1983 by 135 radiation oncologists and 130 physicists. RESULTS: Most respondents were found to work within a multidisciplinary team, consisting of the following specialists (average hours devoted per patient on day of treatment in parentheses): radiation oncologist (3.8), neurosurgeon (3.2), physicist (6.1), radiologist (0.7), nurse (2.7), other (3.0). On average, neurosurgeons and nurses who perform Gamma Knife radiosurgery devote significantly more time-per-patient on the day of treatment than their peers who perform linac radiosurgery. On average, less experienced radiation oncologists and physicists (< or = 24 months experience, or < or = 50 patients treated) devote significantly more time-per-patient on the day of treatment than their more experienced peers. Although there are many more linac radiosurgery facilities than Gamma Knife facilities, on average the number of patients treated per month per facility is significantly larger at the latter. On average, follow-up responsibilities are nearly equally shared by radiation oncologists and neurosurgeons, except at Gamma Knife facilities, where neurosurgeons assume a larger percentage of follow-up responsibility. The percentages of patients treated at linac facilities for metastases or primary CNS malignancy are larger than the corresponding percentages at Gamma Knife facilities; the opposite is true for arteriovenous malformation, acoustic neuroma, and meningioma. CONCLUSION: Current radiosurgery practice usually involves a team approach, with participation of specialists from radiation oncology, neurosurgery, physics, radiology, and nursing. The average number of M.D. and Ph.D. hours required per treatment on the day of radiosurgery is high.

Canada↗
PubMed1994

Respiratory manifestations of rigid spine syndrome.

Thoracic abnormalities and respiratory muscle function were investigated in nine patients with rigid spine syndrome. A severe restrictive chest wall defect and limited mobility of the spine associated with clinically significant respiratory muscle weakness were present in all patients. Respiratory muscle strength and endurance were less than 60% of control values. Slight to moderate scoliosis was present in five patients and absent in four. Scoliosis appeared to have only a minor additional effect on respiratory muscle function. Six patients were emaciated, and one patient was underweight, but no relationship was seen between body mass index and respiratory muscle strength. Respiratory muscle function was more impaired in patients with hypoventilation than in normocapnic patients. Respiratory muscle involvement appears to be a significant feature of rigid spine syndrome, terminating in hypercapnic ventilatory failure in some patients.

Adolescent↗
PubMed1994

[Cysts of second branchial cleft: review of 32 operated cases].

The aim of this work was to analyze retrospectively the clinical features of 32 patients aged 23.9 years (21 female) with the histological diagnosis of second branchial cleft cyst. In 28 patients, the cyst was localized below the mandibular angle. The presenting symptom was a cervical tumor in 30 patients and pain in eight. Fourteen aspiration punctures was performed obtaining 8 purulent and 6 straw colored aspirates. The preoperative diagnosis was correctly made in only 19 patients; the principal confounding diagnosis was tuberculous adenitis. All patients were operated performing a complete cystectomy in 30 and partial cystectomy in two. Three patients had a surgical wound infection and the cysts recurred 5 months and 4 years after operation in the two patients subjected to partial cystectomy. The histological study revealed squamous epithelial with underlying lymphoid tissue. It is concluded that aspiration puncture is useful for the correct diagnosis and that the cyst must be completely eradicated to avoid recurrences.

Adolescent↗
PubMed1994

Membrane-permeant derivatives of cyclic AMP optimized for high potency, prolonged activity, or rapid reversibility.

A novel membrane-permeant derivative of cAMP, cAMP acetoxymethyl ester (cAMP/AM), was synthesized via silylated intermediates. Its ability to induce Cl- secretion by T84 cells, a human colon cancer cell line, was compared with that of two other membrane-permeant cAMP derivatives that were recently introduced, N6,O2'-dibutyryl-cAMP acetoxymethyl ester (bt2cAMP/AM) and Sp-5,6-dichlorobenzimidazole-1-beta-D-ribofuranoside 3',5'-cyclic phosphorothioate (Sp-5,6-DCl-cBIMPS). All of these compounds are powerful activators of Cl- secretion when applied extracellularly, with EC50 values of 60 microM, 0.7 microM, and 3 microM, respectively. However, cAMP/AM was expected to be readily degraded inside cells, in contrast to the cyclophosphodiesterase-resistant Sp-5,6-DCI-cBIMPS or the only slowly metabolizable N6-butyryl-cAMP derived from bt2cAMP/AM. Reversibility of cAMP/AM action was demonstrated by wash-out experiments; Cl- secretion induced by high doses of cAMP/AM (100 microM) could be quickly abolished by rinsing of the cells, whereas similar experiments with bt2cAMP/AM and Sp-5,6-DCI-cBIMPS showed much slower decreases. Even more sensitive to residual cAMP derivatives was the synergistic effect of carbachol, which was applied after the incubation with membrane-permeant derivatives and their subsequent wash-out. Although doses of cAMP derivatives that barely activated Cl- secretion were readily capable of inducing a synergistic response with carbachol, cells incubated with high doses of cAMP/AM (100 microM) and subsequently washed showed only a nonsynergistic carbachol response, in contrast to cells incubated with bt2cAMP/AM or Sp-5,6-DCI-cBIMPS. We therefore characterize cAMP/AM as a membrane-permeant derivative of cAMP that is easily metabolizable inside cells and hence is most useful for applications where a transient intracellular cAMP signal is desired. In contrast, completely nonmetabolizable Sp-5,6-DCI-cBIMPS seems to be more useful in longer incubations that require steady levels of cAMP-dependent protein kinase activation. bt2cAMP/AM combines the advantages of intracellular trapping by ester hydrolysis and reduced cyclophosphodiesterase sensitivity of its active intracellular product, which probably lead to its particularly high potency.

Cell Membrane↗
PubMed1993

Secondary structure and temperature-induced unfolding and refolding of ribonuclease T1 in aqueous solution. A Fourier transform infrared spectroscopic study.

The secondary structure of ribonuclease T1 (RNase T1) in aqueous solution and its temperature-induced structural changes have been investigated by Fourier-transform infrared (FT-IR) spectroscopy. 13 to 14% alpha-helix and 32 to 33% beta-sheet were estimated from the resolution-enhanced FT-IR spectra, in agreement with the crystal structure which indicates 16% alpha-helix and 35% beta-sheet. Specific IR-marker bands are assigned to the different beta-sheet structures, to the slightly bent alpha-helix, and to beta-turn and irregular conformations present in RNase T1. The temperature dependence of the infrared spectra shows that the thermal unfolding and refolding of RNase T1 is fully reversible. This permitted the detailed analysis of structural changes that occur as a function of temperature by evaluating quantitatively the various secondary structure-related amide I band components and some amino acid side-chain vibrations as specific monitors. The secondary structure of RNase T1 is essentially retained in the temperature range between 20 and 50 degrees C. Significant perturbation of protein structure is initiated between 50 and 55 degrees C within regions of beta-sheet structures while the alpha-helix remains virtually intact up to 55 degrees C suggesting a "premelting" of RNase T1. Between 55 and 60 degrees C, a highly co-operative unfolding process is indicated by the simultaneous breakdown of all secondary structure components and by distinct changes of some specific side-chain vibrations. An analysis of the amide I band contour of RNase T1 at 70 degrees C proves that the unfolded state is predominantly, but not completely, irregular or "random coil". Residual, turn-like structures persisting even in the unfolded state are suggested by minor, turn related band components in the amide I region. From IR-spectra collected along a linear temperature gradient, intensity/temperature and frequency/temperature profiles were constructed using some peptide backbone and amino acid side-chain marker bands as local, structure-sensitive monitors. From these profiles individual transition temperatures tm and transition enthalpies delta H (van't Hoff) were calculated. The tm and delta H values revealed a small but distinct hysteresis between repetitive cycles of unfolding and refolding of the protein, suggesting slow refolding kinetics of RNase T1. Furthermore, the various infrared "marker bands" indicate a slightly different response towards temperature increase/decrease for different regions of the protein. The data demonstrate that infrared spectroscopy permits both the detailed analysis of structural changes occurring in a protein as a function of temperature and the determination of thermodynamic parameters characterizing its folded/unfolded state transition.

Amides↗