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Biomedical subjects

M Frick

Publications and source records attributed to M Frick.

At least 37 records · Page 2Linked to original sources
PubMed1998

Long-term induction of a unique C1- current by endothelin-1 in an epithelial cell line from rat lung: evidence for regulation of cytoplasmic calcium.

1. Using conventional microelectrodes, the perforated patch clamp technique and fluorescence microscopy with fura-2, we investigated the relationship between the cell membrane potential, whole-cell currents and the free cytoplasmic Ca2+ concentration ([Ca2+]i) in response to 10 nM endothelin-1 (ET) in a rat respiratory epithelial cell line (L2). 2. Microelectrode experiments revealed that ET caused an immediate depolarization of the cell membrane potential (Vm) by 25 mV, which was unaffected by Na+ replacement with N-methyl-D-glucamine+ (NMDG+) or by omission of bath Ca2+. In contrast, ET depolarized the cells by 61 mV in the presence of low C1- (6 mM), resulting in a complete breakdown of Vm. 3. In perforated patch clamp experiments, the ET-induced whole-cell current (IET) exhibited a slight outward rectification with a reversal potential (Vrev) of -22.7 mV. IET was reduced by 85 % in low C1- (6 mM), but was unaffected by Ca2+ removal, Na+ replacement with NMDG+, pipette K+ replacement with Cs+ or 1 mM Ni2+ in the bath. 4. IET was unaffected by (+)-isradipine (100 nM), a specific L-type Ca2+ channel (L-VDCC) blocker. Transient inward Sr2+ currents through L-VDCCs were blocked by ET. 5. ET induced a biphasic Ca2+ signal, consisting of a 'peak' and a 'plateau' elevation of [Ca2+]i. Simultaneous patch clamp and fura-2 measurements revealed that IET coincided with intracellular Ca2+ release but clearly outlasted the elevation of [Ca2+]i. When the rise of [Ca2+]i was prevented by pretreatment with thapsigargin in a Ca2+-free bath, both activation time and amplitude of IET were reduced. Under these conditions, ET caused a decrease of [Ca2+]i. 6. The C1- channel blocker mefenamic acid (MFA) had a dual, concentration-dependent effect on both IET and the ET-induced 'plateau' elevation of [Ca2+]i: an increase at 10 microM, but an almost complete block at 100 microM. The effect of MFA on IET preceded the effect on [Ca2+]i. 7. The ET-induced 'plateau' [Ca2+]i fell below control values in a low-C1- (6 mM) solution. 8. These data indicate an amplifying function of intracellular Ca2+ release on an otherwise Ca2+-independent, unique C1- current by ET. Moreover, this C1- current appears to be functionally coupled with dihydropyridine (DHP)-insensitive Ca2+ entry, suggesting a modulatory role for long-lasting effects of ET.

Animals↗
PubMed1998

[Studies with high-dose chemotherapy and subsequent autologous stem cell transplantation in breast carcinoma].

Survival rates for several subgroups of patients with breast cancer treated with conventional therapy remain poor. Only about 30% of patients with primary breast cancer involving more than 9 axillary lymph nodes remain disease-free at 5 years from diagnosis despite surgery, conventional-dose chemotherapy and radiotherapy. Metastatic breast cancer with 5 year survival rates of about 3% generally represents incurable disease. Chemotherapeutic agents are conventionally limited by side effects. The easy procurement of haematopoietic stem cell support through mobilization of peripheral blood progenitors has spurred the development of new strategies employing high-dose treatment for treatment of high risk breast cancer. Autologous stem cell support antagonizes chemotherapy-induced myelotoxicity and thereby allows dose escalation by a factor of 1.5 to about 20. Pilot studies evaluating significant dose escalation in adjuvant treatment of patients with advanced disease have resulted in an apparent improvement in event-free survival rates to over 70%. Repetitive applications of chemotherapy at myeloablative doses are now increasingly being used. Data from prospectively randomized phase III trials will not be available before the end of 1998. For metastatic breast cancer one prospective, randomized clinical trial has been published. Results are significantly better for patients who have been treated by high-dose chemotherapy compared to patients who received conventional polychemotherapy (median survival 90 vs. 45 weeks). For methodological reasons (small patient numbers, patient selection, weak standard therapy etc.) results from the trials cited above are under discussion. Until publication of further results from ongoing phase III trials HDC for breast cancer remains experimental and should not be given outside of clinical trials.

Antineoplastic Agents↗
PubMed1997

[Significance of stem cell-supported high-dose chemotherapy in the treatment of gynecological malignancies: indications and current clinical trials in the Federal Republic of Germany].

The use of hematopoetic growth factors and stem cell support reduces the dose limiting hematopoetic toxicity's, resulting in a remarkable increase in dose intensity of chemotherapy. As far as data from phase I/II trials are available high dose chemotherapy (HDC) may be integrated in the systemic treatment of breast and ovarian cancers. In metastatic breast cancer HDC may induce fairly high but short response rates. Long term survival is expected in 20% of the cases. Patients with limited metastatic disease, without significant prior chemotherapy, partial or complete response to induction chemotherapy and complete remission after HDC may benefit from HDC. In phase I/II trials HDC improved recurrence free survival in high risk patients (e.g. > 9 positive LN) compared to historic controls and may therefore be a curative approach. Ovarian cancer is very chemosensitive. Conventional chemotherapies induce multidrug resistance rapidly. Just as in breast cancer-Phase I/II trials demonstrated high response rates to HDC, which again were short of duration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Idarubicin, melphalan and cyclophosphamide: an intensified high-dose regimen for the treatment of myeloma patients.

Following conventional chemotherapy, eight myeloma patients presenting with advanced tumor stages were treated with an intensified high-dose regimen and autologous peripheral blood stem cell transplantation. High-dose chemotherapy consisted of idarubicin 20 mg/m2 on days -13, -12 and -11, melphalan 100 mg/m2 on days -5 and -4 and cyclophosphamide 60 mg/kg (plus mesna 60 mg/kg) on days -3 and -2 (IMC). Seven patients achieved a complete remission or a very good partial remission (reduction of M-component > or =90%). There were no toxic deaths. Severe mucositis and fever of unknown origin were seen in all patients. Reversible supraventricular tachycardias without clinical signs of cardiac failure occurred in five patients. One patient developed a persistent deterioration of cardiac function. We surmise that high-dose chemotherapy with IMC is very effective and well tolerated in myeloma patients.

Adult↗
PubMed1991

Identification and characterization of proteinase K-resistant proteins in members of the class Mollicutes.

Proteins resistant to proteinase K are rare because of the potency, wide pH optimum, and low peptide bond specificity of this enzyme. Previously, only the prion proteins associated with transmissible spongiform encephalopathies, possibly related proteins in the mollicute Spiroplasma mirum, and proteinase K itself have been reported. We identified a new proteinase K-resistant protein, p40-pr, in two strains of Mycoplasma hyorhinis and in extracts of these organisms. p40-pr's are similar to prion proteins in their resistance to high doses of proteinase K and in the reversal of this resistance by strong denaturing conditions. However, p40-pr's were distinct immunologically, in relative molecular mass, and in their method of extraction. Two immunologically related forms of p40-pr were identified on sodium dodecyl sulfate (SDS) gels and Western immunoblots, a 40-kDa species in boiled samples and a 120-kDa species dissociable by boiling in SDS. Reduction with 2-mercaptoethanol did not affect the mass of p40-pr's or the 120-kDa forms. The development of proteinase K resistance of p40-pr correlated to age-dependent increases in organism protein-lipid ratios. p40-pr-like proteinase K-resistant proteins of 46 to 50 kDa were identified in four of eight additional species of the class Mollicutes but not in S. mirum. However, these mycoplasmal proteins did not react with antibody to the denatured 40-kDa form of M. hyorhinis p40-pr purified by electroelution. The chromatographically purified 46-kDa proteinase K-resistant protein of Mycoplasma orale was an arginine deiminase.

Animals↗
PubMed1990

Involvement of older drivers in multivehicle side-impact crashes.

Side impacts were studied using three separate analyses. National Accident Sampling System (NASS) and National Crash Severity Study (NCSS) cases were reviewed on multivehicle crashes involving fatal chest and abdominal injury by interior contact. Twenty-five cases were analyzed and showed an unusually high involvement of older occupants. Analyses of the 1975-1986 FARS confirmed an overinvolvement. Sixty-four percent of near-side seated occupants were over 50 years old and 36% over 70 in fatal multivehicle side impacts. In contrast, 26% of victims in single-vehicle frontal crashes were over 50 and 8% over 70 years old. Analysis of the 1982-1986 NASS showed that single-vehicle side impacts are not an important injury risk for older drivers, except on icy or wet roads. In contrast, the risk of injury in multivehicle side impacts increases steadily with age and is a major problem for older drivers. The individual NASS and NCSS cases also showed that 88% of the multivehicle side crashes took place at an intersection and that the driver of the struck vehicle frequently caused the crash by driving error (48%) or traffic violation (16%). The majority of cases occurred in daylight hours, on dry roads, and without alcohol involvement. Changes in visual perception, judgment and attention of the older driver may be factors in their missing a traffic signal or turning in front of traffic under the right-of-way. In addition, a reduced tolerance to impact force probably contributes to the injury. Although an analysis of photographs of the side-impacted vehicle indicated that 44% had side-structure deformation that was similar to that produced in the National Highway Traffic Safety Administration (NHTSA) moving deformable barrier test, only 24%-32% of the cases actually addressed the proposed NHTSA dynamic side-impact test. The results of this analysis bear on the agency's preliminary regulatory impact analysis.

Abdominal Injuries↗
PubMed1987

Separation of multiple components of HeLa cell nuclear extracts required for pre-messenger RNA splicing.

Components essential for nuclear pre-messenger RNA splicing have been partially purified from HeLa cell nuclear extracts by chromatography on DEAE-Sepharose, heparin-Sepharose, Mono Q, and Mono S. We have obtained six fractions which, when combined, efficiently splice a synthetic adenovirus 2 major late RNA substrate in vitro. All fractions contain components that support the formation of splicing intermediates (the cleaved 5' exon and the intron-exon 2 lariat). At least one of the fractions also contains an activity that is essential for the second step in the splicing reaction, namely cleavage at the 3' splice site and exon ligation. Two of the fractions are enriched in the major small nuclear ribonucleoprotein particles U1, U2, U4/U6, and U5. They participate in the formation of the splicing complexes which precedes the cleavage and ligation reactions. The remaining four fractions appear to contain protein factors, as suggested by their resistance to micrococcal nuclease.

Chromatography, Gel↗
PubMed1987

Local antibodies to alpha-casein and beta-lactoglobulin in the saliva of infants.

Salivary antibodies were studied in 112 infants between 1 day and 8 yr of life. SIgA anticasein was present from birth in breast-fed and bottle-fed infants. Bottle-feeding resulted in significantly higher concentrations of SIgA anticasein at 3 wk to 3 months of life as compared to breast-feeding. Salivary anticasein declined toward the end of the 1st yr and was present in less than half of the children older than 1 yr. Salivary anti-beta-lactoglobulin was also present at birth in some infants. Levels increased slightly over the following 3 months but remained low. Only a minority of older children had this antibody in their saliva.

Animals↗
PubMed1984

Opiate induced feeding is not dependent on the hippocampus.

It has been shown that spreading depression of the hippocampus can elicit feeding, and that several opioid peptides elicit spreading depression when injected into the hippocampus. To determine whether such depression is the primary mechanism by which opiates induce feeding, we tested the feeding effects of naloxone, an opiate antagonist, and butorphanol tartrate, a kappa-sigma agonist, on feeding in rats with and without hippocampal lesions. Naloxone tended to reduce intake approximately equally in the two groups. Similarly, the doses of butorphanol that increased intake in sham rats were equally effective in lesioned rats. It was concluded that the hippocampus is not the major structure mediating opiate-induced feeding.

Animals↗
PubMed1984

Selective localization of the parathyroid secretory protein-I/adrenal medulla chromogranin A protein family in a wide variety of endocrine cells of the rat.

Secretory protein-I (SP-I) of parathyroid glands and chromogranin A ( CGA ) of adrenal medullary chromaffin cells are chemically similar if not identical proteins. Both proteins are contained within secretory granules and appear to be cosecreted with granule contents, for example, in the parathyroid with PTH and in the adrenal with epinephrine and dopamine beta-hydroxylase. Antisera to bovine SP-I and porcine CGA , together with antisera to a variety of peptide hormones, were used in an immunofluorescence study of rat tissues in order to determine the probable distribution and cellular localization of these proteins. In addition to their previously demonstrated presence in parathyroid and adrenal cells, the SP-I/ CGA protein family was detected in cells of the thyroid that contained calcitonin and often SRIF but not thyroglobulin; in cells of the anterior pituitary staining for the alpha-subunit of TSH/FSH/LH but not in cells staining for GH, PRL, ACTH, or beta-endorphin; in pancreatic islet cells staining for SRIF and pancreatic polypeptide-related peptides, but not for insulin or glucagon; in the celiac and mesenteric ganglia in cells some of which contained SRIF; and in the gastric antrum in cells containing SRIF, but not gastrin. SP-I/ CGA was not detected in cells of the liver, kidney, parotid gland, or acinar pancreas or in the intermediate or posterior lobes of the pituitary. These results suggest that this protein family enjoys a widespread but highly restricted distribution in many different endocrine-peptide cells of the rat, many that are believed to be of the APUD cell series. The possibility is raised that SP-I/ CGA plays some physiological role in the secretory process or exerts an effect of its own in the periphery after secretion.

Adrenal Medulla↗
PubMed1983

[Fractures of the tuberculum intercondyloideum laterale in children].

Thirty-one fractures of the tibial spine in children have been treated, two of them being old fractures. They were reviewed after a minimum follow-up of six months and a maximum of seven years. Ten were treated conservatively, 21 operatively. The mechanism is discussed. The trauma is described as either a posterior displacement of the femoral condyle or rotation and abduction of the leg with the knee flexed. The importance of testing stability under general anaesthesia is stressed. Sixteen cases had an anterior drawer sign. The medical meniscus was only injured in one case. The indications for treatment are: Conservative treatment should be given in fractures without displacement and without instability. All other types should be treated surgically with fixation of the anterior cruciate ligament made through a tunnel in the tibia. Whichever type of treatment is used, the length of immobilisation in plaster should not exceed 30 days. Twenty-seven cases were available for study. Twenty-three had excellent results, three good results and one poor result.

Adolescent↗
PubMed1982

Obstructing esophageal hematoma mimicking cancer: a case report and experimental study.

In this paper the 10th case of esophageal hematoma, a rare variant of the Mallory-Weiss syndrome, is reported. The radiographic study strongly suggested an obstructing neoplasm, however, this hematoma disappeared within five days and this same rapid disappearance was noted in dogs in which esophageal hematomas were induced. Fiberoptic esophagoscopy provides a clue to the diagnosis since the mural hematoma is differentiated from carcinoma by its dark color.

Aged↗
PubMed1981

Distribution of methionine-enkephalin immunoreactivity in the chick brain: an immunohistochemical study.

The distribution of Met-enkephalin-like immunoreactivity in the brains of 2-week-old domestic chicks was studied with immunohistofluorescence and the unlabeled antibody peroxidase-antiperoxidase technique, using antibodies to Met-enkephalin generated in rabbits. Immunoreactive cell bodies were found in the telencephalon, diencephalon, and mesencephalon in areas as yet uncharacterized as discrete nuclei in birds (E-1, E-2, E-3, E-4, E-5); further cells were located in the diencephalic nucleus spiriformis lateralis, the midbrain medial intercollicular nucleus (E-6), the nucleus mesencephalicus lateralis, pars dorsalis, the Edinger-Westphal nucleus and dorsal occulomotor nucleus; and in the nucleus of cranial nerve X and an uncharacterized area in the dorsolateral medulla (E-7). Immunoreactive fibers and/or terminals were located around the immunoreactive cell bodies and, in addition in the lateral septal area of the telencephalon; in the preoptic and hypothalamic areas of the diencephalon; in the anterior intercollicular area, periaqueductal central gray, area C, and the midventral tegmentum of the mesencephalon; in the nucleus solitarius, nucleus IX-X, nucleus intercalatus, nucleus intermedius, and ventrolateral areas of the rhombencephalon. The pattern of distribution of met-enkephalin in the chick is compared with that in the rat. A possible functional role for Met-enkephalin in neural mechanisms mediating some behaviors of the chick is suggested.

Animals↗