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Biomedical subjects

S Keller

Publications and source records attributed to S Keller.

At least 19 recordsLinked to original sources
PubMed1996

Tissue-specific isoforms of chicken myomesin are generated by alternative splicing.

Myomesin is a high molecular weight protein that is present in the M-band of all fiber types of cross-striated skeletal muscle and heart. We have isolated two cDNAs encoding tissue-specific isoforms of chicken myomesin with calculated molecular masses of 174 kDa in skeletal muscle and 182 kDa in heart. Distinct sequences are found at the 3'-end of the two cDNAs, giving rise to different C-terminal domains. Partial analysis of the gene structure has shown that in chicken, both isoforms are generated by alternative splicing of a composite exon. Amino acid sequences show that the main body of myomesin consists of five fibronectin type III (class I motifs) and seven immunoglobulin-like domains (class II motifs). An identical structure was found in M-protein and human 190K protein (the human counterpart of chicken myomesin), and a comparable domain arrangement occurs in the M-band-associated protein skelemin. We postulate that myomesin, M-protein, and skelemin belong to the same subfamily of high molecular weight M-band-associated proteins of the immunoglobulin superfamily and that they probably have the same ancestor in evolution.

Alternative Splicing↗
PubMed1996

Spontaneous pneumothorax in the AIDS population.

Spontaneous pneumothorax (SP) in patients with acquired immunodeficiency syndrome (AIDS) has become the leading cause of nontraumatic pneumothorax in the urban population. However, the appropriate treatment, especially the role of surgical intervention, remains controversial. A retrospective study of 33 patients with AIDS who were treated for 38 episodes of SPs (5 bilateral SPs) at our institution was conducted. The study consisted of 25 males (76%) and 8 females (24%) with a mean age of 38 years. Concurrent Pneumocystis carinii pneumonia was detected in 29/33 patients (88%). Three forms of treatment were utilized for the 38 pneumothoraces (5 of which required two modalities): closed tube thoracostomy, 28/38 (group 1); observation alone, 10/38 (group 2); and operative procedures, 5/38 (group 3). There were eight hospital deaths, four following resolution of the SP. Follow-up was available for 14 patients, 11 of whom died a median of 3 months post-discharge. Three patients were alive 1, 3, and 18 months post-discharge. AIDS-related SP is strongly associated with Pneumocystis carinii pneumonia and is predictive of a short-term survival. The treatment should be individualized, and, although resolution of the pneumothorax can be expected, the coexisting AIDS-related illnesses determine the outcome.

AIDS-Related Opportunistic Infections↗
PubMed1995

Quantity and quality of venom released by a spider (Cupiennius salei, Ctenidae).

The amount of venom injected by the spider Cupiennius salei depended on the efficiency of the mechanical defence of the prey species. Spiders were milked for the first venom (i.e. the first microlitre of venom emitted) versus remaining venom, and for venom regenerated from emptied glands. HPLC gel filtration and IEF electrophoresis showed that the protein content of the first venom was only half as compared to that of the remaining venom, and that this was due to a dilution of all proteins. Venom regeneration came in two speeds. The amount of venom was regenerated more rapidly than the protein concentration. Newly regenerated venom as compared to older venom was characterized by a lower concentration of all proteins and by a higher total concentration of free amino acids, whereas histamine and taurine did not follow this trend. K+ concentration and pH remained similar during venom regeneration. Crickets injected with the venoms showed less acute symptoms when the protein concentration was lower, namely with the first venom and with newly regenerated venom. Consequently, a spider which modulates the quantity of venom injected into a prey also directly changes the venom quality. The ecological consequences of this are discussed. This paper also discusses which region of a gland (ampulla, extracellular and intracellular parts of the glandular sac) is involved in the changes of the venom quality.

Amino Acids↗
PubMed1995

Acute promyelocytic leukemia.

Significant advances have occurred in the diagnosis, treatment, and long-term outcome of patients with acute promyelocytic leukemia (APL). The purpose of this review is to describe the molecular genetics of this disease, the use of all-trans retinoic acid (ATRA) in clinical trials of APL, and the clinical and basic research questions for future investigation. Findings of clinical studies in mainland China using ATRA as induction therapy for patients with APL concurrent with laboratory characterization of the molecular changes in APL have led to worldwide clinical trials of ATRA in the treatment of patients with APL. Major advances in understanding the molecular biology and genetics of APL have occurred over the past 5 years. These findings have been translated into novel treatment strategies using all-trans retinoic acid as a differentiation agent in the induction phase of therapy resulting in improved long-term outcome, reduced morbidity, and lower costs for patients with APL. Advanced molecular techniques are being employed for diagnosis and for monitoring of patient response to treatment.

Child↗
PubMed1994

Survival following resection of clinically occult N2 non small cell lung cancer.

BACKGROUND: The role of resection in Stage IIIA (N2) non-small cell lung cancer (NSCLC) remains controversial despite reported survival rates of 25-40%. This study was undertaken to identify factors associated with a high risk of treatment failure after resection of clinically occult Stage IIIA (N2) NSCLC: Such prognostic factors may identify high risk patients as candidates for future clinical trials of multimodality lung cancer treatment and be important stratification factors in such trials. METHODS: The clinical and pathological records of 32 patients with clinical NO pathologic N2 NSCLC who underwent lobectomy (n = 17), pneumonectomy (n = 12), or bilobectomy (n = 3) and complete mediastinal lymph node dissection at Fox Chase Cancer Center from 1987 to 1991 were reviewed. A multivariate analysis of clinical and pathologic variables was performed. RESULTS: Median follow-up was 15 months (range 5-55). Fifty-nine percent have recurred and 44% have died. Median disease free and overall survival were 16 and 19 months, respectively. Two year disease free and overall survival were 24% and 43%, respectively. No patient with more than one level of mediastinal lymph node metastases survived two years free of disease. Univariate and multivariate analysis revealed a longer disease free survival for those receiving adjuvant radiation therapy (19 vs 5 months) but no increase in overall survival. CONCLUSIONS: This experience with clinically occult Stage IIIA (N2) NSCLC suggests that multiple levels of mediastinal lymph node metastases predict treatment failure in patients following resection and that adjuvant mediastinal radiation improves disease free but not overall survival.

Adult↗
PubMed1994

Analysis of elastin cross-linking and the connective tissue matrix of abdominal aortic aneurysms.

BACKGROUND: Studies of the connective tissue matrix of abdominal aortic aneurysms (AAAs) have yielded conflicting results, and the glycosaminoglycan content has not been previously reported. The present work was done to evaluate the matrix components of AAAs, including the cross-link content of the residual elastin. METHODS: Aortic specimens from AAAs and controls were sequentially extracted with salt, Brij, and urea; and the residual pellets were the subject of further studies. Elastin was purified by hot alkali treatment; other matrix components were determined by conventional methods. RESULTS: Elastin content of the purified material was reduced in AAA. The cross-link content, desmosine+isodesmosine, was also reduced in AAA as a ratio to insoluble matrix dry weight. However, the cross-link content as a ratio to valine in the purified elastin was normal. The amino acid profiles of representative AAA and controls elastin preparations were similar to that of reference elastin. The amino acid content of the insoluble matrix of AAA revealed a significant reduction of protein (controls = 820 +/- 40 micrograms/mg versus AAA = 700 +/- 20 micrograms/mg, p < 0.05); the collagen content was unaltered. The content of glycosaminoglycan in AAA was noted to be significantly reduced (controls = 33.5 +/- 3.4 micrograms/mg versus AAA = 17.1 +/- 2.0 micrograms/mg, p < 0.05). CONCLUSIONS: The data do not support the hypothesis of a primary cross-link deficiency in elastin of AAA; but the reduced contents of protein and glycosaminoglycans in AAA suggests basic biochemical alterations in the diseased aorta that warrant further investigation.

Amino Acids↗
PubMed1992

International Quality of Life Assessment (IQOLA) Project.

The International Quality of Life Assessment (IQOLA) Project is a 4-year project to translate and adapt the widely used MOS SF-36 Health Survey Questionnaire in up to 15 countries and validate, norm, and document the new translations as required for their use in international studies of health outcomes. In addition to the eight-scale SF-36 health profile, the project will also validate psychometrically based physical and mental health summary scores, as well as health utility indexes incorporating SF-36 scales for use in cost-utility studies.

Europe↗
PubMed1992

Should patients with post-resection locoregional recurrence of lung cancer receive aggressive therapy?

The outcome of thirty-seven patients with a post-resection locoregional recurrence of non-small cell lung cancer treated with radiation therapy alone between 1979 and 1989 was compared to that of 759 patients with unresected non-small cell lung cancer also treated with standard radiation during the same period. Each patient's locoregional recurrence was staged using the current American Joint Committee on Cancer staging system. Comparison of pretreatment characteristics between the two groups, including age, sex, extent of weight loss, performance status, stage, and histologic subtype revealed fewer patients with greater than 5% weight loss (35 vs. 47%, p = 0.04) and more cases with squamous histology (54 vs. 28%, p = 0.01) among the patients with locoregional recurrences than those with newly diagnosed lesions. Over 80% of both groups had clinical stage III lesions. The median radiation doses were 56 and 59 Gy for recurrent and newly diagnosed cases (p = NS). For the patients with locoregional recurrences, the median time from resection to recurrence was 13 months (range: 3-118 months), and the recurrences were predominantly nodal in 25 cases, chest wall/pleural in four and at the bronchial stump in eight. When measured from the date of documented recurrence, the median survival time and 2-year actuarial survival rate of the patients with recurrent lesions were 12 months and 22%, as compared to 12 months and 26% for the newly diagnosed patients (p = NS). Freedom from documented locoregional tumor progression at 2 years was 30% for both groups. Patients with bronchial stump lesions had superior survival to those with nodal or chest wall recurrences, with a median survival time of 36 versus 9 months. A therapeutic approach to selected patients with post-resection locoregional recurrence of non-small cell lung cancer equally aggressive to that for newly diagnosed lung cancer patients is justified by these results, especially for patients with bronchial stump recurrences.

Adult↗
PubMed1990

Polar surface distribution of type II insulin-like growth factor receptor in rat hepatocytes.

We describe the distribution of type II insulin-like growth factor receptors among canalicular (cLPM) and basolateral (bLPM) subfractions of rat liver plasma membranes (LPM). BLPM bound 3 times more 125I-IGF II than cLPM. The number of receptors was (1.3 +/- 0.15) X 10(-12) mol/mg in bLPM, and (0.4 +/- 0.17) X 10(-12) mol/mg in cLPM. Insulin-like growth factor II (IGF II) was 10 times more potent than insulin-like growth factor I (IGF I) in displacing 125I-IGF II from both basolateral and canalicular binding sites. Insulin did not interfere with binding of 125I-IGF II in either LPM preparations. Our findings point to an asymmetrical hepatocellular distribution of type II IGF receptors, thus extending the concept of surface polarization of hepatocytes to growth promoting hormone receptors.

Animals↗
PubMed1990

The effect of 60% oxygen on air-space enlargement and cross-linked elastin synthesis in hamsters with elastase-induced emphysema.

Hyperoxia is routinely administered to patients with severe emphysema. To gain insight into the possibly adverse effects of such treatment, hamsters were exposed to 60% oxygen for 5 days, beginning 48 h after induction of pulmonary emphysema by intratracheal instillment of pancreatic elastase. Control groups consisted of (1) animals instilled with elastase and exposed to room air, (2) animals instilled with saline and exposed to 60% oxygen, and (3) animals instilled with saline and exposed to room air. Cross-linked elastin content and synthesis in the lung were measured immediately following termination of hyperoxia, and the mean linear intercept was determined 4 wk later. Cytologic examination of bronchoalveolar lavage fluids was also performed. Statistical significance was determined by a two-way analysis of variance. Results indicate that exposure to 60% oxygen significantly affected (p less than 0.05) air-space size, causing a 51% increase among elastase-treated hamsters (124 versus 82 microns) but only a 4% increment among saline-treated animals (52 versus 50 microns). When compared to other groups, animals treated with both elastase and hyperoxia had a significantly greater (p less than 0.01) percentage of neutrophils (28%) in their lung lavage fluids immediately following exposure to 60% oxygen. Although total lung elastin content was not altered by hyperoxia at this time, labelling of elastin cross-links was significantly increased (p less than 0.05). These studies demonstrate that exposure to 60% oxygen enhances elastase-induced lung injury. They also raise the possibility that oxygen therapy may, under certain circumstances, accelerate the progression of human emphysema.

Animals↗
PubMed1989

Effect of insulin on glucose transporter distribution in white fat cells from hypophysectomized rats.

Glucose transport in white fat cells from hypophysectomized rats is increased and unresponsive to insulin. The goal of this study was to explain this observation. The number of glucose transporters, as determined by D-glucose-inhibitible cytochalasin B binding, in the plasma membranes from fat cells of hypophysectomized rats is: (1) elevated, (2) not increased by insulin, and (3) the same as in plasma membranes from insulin-stimulated fat cells of control rats. In microsomal membranes from fat cells of hypophysectomized rats the number of glucose transporters is: (1) smaller than in basal and insulin-stimulated fat cells from control rats, and (2) not changed by insulin.

Adipose Tissue↗
PubMed1989

Growth of aneurysms can be understood as passive yield to blood pressure. An experimental study.

The strength of aneurysm walls obtained intraoperatively or at autopsy immediately after death was evaluated by measurements of the force response to one-directional stretch and compared to the walls of intracranial arteries. The maximum stress that aneurysm tissue could tolerate was found slightly lower than in arteries, which is most probably due to the amount of immature forms of collagen. The stress resistance of aneurysms and arterial tissue decayed over a period of several hours. The relaxation curve could be approximated by the sum of 2 exponential terms. The half decay times of these terms were found identical in aneurysms and arteries, they appear to be collagen characteristics. The strength measured in vitro was compared to the stress in vivo, which was calculated on the basis of blood pressure and aneurysm radius. The stress tolerated by aneurysm walls over a period of 24 hours was found to be in the range of the stress that is imposed in vivo by the mean blood pressure. Arteries resisted stresses corresponding to pressures 10 to 20 times higher than physiological values. The thickness of the aneurysm walls correlated with the aneurysm radius in a linear fashion. It is suggested that aneurysm growth can be understood as passive yield to blood pressure, and reactive healing and thickening of the wall with increasing aneurysm diameter.

Biomechanical Phenomena↗
PubMed1989

Strength, elasticity and viscoelastic properties of cerebral aneurysms.

Tissue strength and stiffness of cerebral aneurysm walls obtained intraoperatively or at autopsy were evaluated by uniaxial strain/stress measurements. For comparison, corresponding measurements were also made on autopsy specimens of intracranial arteries. The maximum stress that the aneurysm tissue could tolerate, the yield stress, was found to be slightly lower than in arteries, which is likely due to the content of immature forms of collagen. The material stiffness, as determined by division of the yield stress by the corresponding strain, was also smaller in aneurysms than in arteries. The stress resistance of aneurysms and arterial tissue decreased over a period of several hours. The relaxation curves were found to be identical in aneurysms and arteries. The stress tolerated by aneurysm walls was found to be in the range of the stress that is imposed in vivo by the blood pressure. Arteries resisted stresses corresponding to pressures 5-10 times higher than physiological values. It is suggested that the balance of tissue strength and the stress imposed by the blood pressure is causally related to aneurysm growth.

Adult↗