RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T lymphocytes

The related adhesion focal tyrosine kinase (RAFTK), a recently discovered member of the focal adhesion kinase family, has previously been reported to participate in signal transduction in neuronal cells, megakaryocytes, and B lymphocytes. We have found that RAFTK is constitutively expressed in human T cells and is rapidly phosphorylated upon the activation of the T cell receptor (TCR). This activation also results in an increase in the autophosphorylation and kinase activity of RAFTK. After its stimulation, there was an increase in the association of the src cytoplasmic tyrosine kinase Fyn and the adapter protein Grb2. This association was mediated through the SH2 domains of Fyn and Grb2. RAFTK also co-immunoprecipitates with the SH2 domain of Lck and with the cytoskeletal protein paxillin through its COOH-terminal proline-rich domain. The tyrosine phosphorylation of RAFTK after T cell receptor-mediated stimulation was reduced by the pretreatment of cells with cytochalasin D, suggesting the role of the cytoskeleton in this process. These observations indicate that RAFTK participates in T cell receptor signaling and may act to link signals from the cell surface to the cytoskeleton and thereby affect the host immune response.     

A neural network approach to job-shop scheduling

A novel analog computational network is presented for solving NP-complete constraint satisfaction problems, i.e. job-shop scheduling. In contrast to most neural approaches to combinatorial optimization based on quadratic energy cost function, the authors propose to use linear cost functions. As a result, the network complexity (number of neurons and the number of resistive interconnections) grows only linearly with problem size, and large-scale implementations become possible. The proposed approach is related to the linear programming network described by D.W. Tank and J.J. Hopfield (1985), which also uses a linear cost function for a simple optimization problem. It is shown how to map a difficult constraint-satisfaction problem onto a simple neural net in which the number of neural processors equals the number of subjobs (operations) and the number of interconnections grows linearly with the total number of operations. Simulations show that the authors' approach produces better solutions than existing neural approaches to job-shop scheduling, i.e. the traveling salesman problem-type Hopfield approach and integer linear programming approach of J.P.S. Foo and Y. Takefuji (1988), in terms of the quality of the solution and the network complexity.     

Tay-Sachs disease in persons of French-Canadian heritage in northern New England

This study sought to determine whether persons of French-Canadian heritage in northern New England are at high risk for the lethal infantile form of Tay-Sachs disease. In order to accomplish this, death records and laboratory diagnostic records were surveyed to ascertain Tay-Sachs deaths in a cohort of 372,000 live births between 1977-1986. The proportion of the total population with French-Canadian or Jewish heritage was determined from census and birth records, and the ethnic background of Tay-Sachs cases was determined from the corresponding birth records. In 1,860 births, both parents were of Ashkenazi Jewish heritage. One of those children was diagnosed with Tay-Sachs disease. In 41,000 births, both parents were of French-Canadian heritage, and in an additional 93,000 births, one parent was of French-Canadian heritage. No cases of Tay-Sachs disease were identified in the offspring of those individuals. Approximately 14 cases (95% confidence interval 8-20) would be expected, if the gene frequency approximated that reported for individuals of Ashkenazi Jewish heritage. Based on the results of this study, routine testing for Tay-Sachs disease heterozygosity is not indicated for persons of French-Canadian heritage in northern New England. This conclusion may not necessarily be valid for persons of French-Canadian heritage residing in other states. Further studies of Tay-Sachs disease mutations and prevalence among persons of French-Canadian heritage will be important to determine possible regional variations in gene frequencies.     

Time-resolved chirp evaluations of Gbit/s NRZ and gain-switched DFB laser pulses using narrowband Fabry-Perot spectrometer

A compact, easy-to-use, low-cost spectrometer for solving the chirped spectrum of DFB lasers is demonstrated using narrowband Fabry-Perot etalons with resolutions comparable to grating spectrometers. Time-resolved chirp measurements of Gbit/s NRZ and gain-switched DFB laser pulses are presented.<>     

Can radioactive iodine be used in the treatment of diffuse non-toxic goiter?

Traditional treatment modalities of diffuse nontoxic goitre are thyroid hormone suppression or surgery. When treating nodular nontoxic goitre with 131I treatment, a reduction in thyroid volume to about 50% is seen. In the present study we evaluated the effect of 131I treatment in 21 patients treated for a diffuse nontoxic goitre and followed by evaluation of thyroid volume measured by ultrasound. Thyroid volume declined in all patients from median of 66 ml (range 27-160 ml) to 21 ml (9-108 ml) over a year, a reduction of 62%. Three patients developed hypothyroidism in the follow-up period (14%), one of these had a temporary hyperthyroid fase. In conclusion, 131I treatment of diffuse nontoxic goitre reduces thyroid volume by approximately 60% within 12 months. Hypothyroidism developed in 14% during a limited follow-up period.     

Adaptive functioning following traumatic brain injury and orthopedic injury: a controlled study

BACKGROUND: In an effort to intensify osteosarcoma therapy, systemic ifosfamide was added pre- and postoperatively to an already aggressive three-drug regimen. In a subgroup of patients, loco-regional treatment intensification was attempted by using the intraarterial route to give cisplatin. PATIENTS AND METHODS: Patients < or = 40 years at diagnosis of a localised, de novo high-grade central extremity osteosarcoma were eligible for inclusion into study COSS-86 if registered within three weeks from biopsy. Doxorubicin, high-dose methotrexate, and cisplatin were given to all patients. Patients who fulfilled one or more of three defined high-risk criteria received early systemic treatment intensification by adding ifosfamide as the fourth agent. Preoperatively, these high-risk patients received cisplatin either intraarterially or intravenously. RESULTS: 171 eligible patients were entered, of which 128 were stratified into the high-risk group. When all 171 were analysed by intention-to-treat, actuarial overall and event-free survival rates at ten years were 72% and 66%, respectively. No benefit of intraarterial cisplatin application was detected. Cumulative treatment toxicity was considerable. CONCLUSIONS: In a multicenter setting, intensive treatment of osteosarcoma according to protocol COSS-86 led to long-term disease-free survival for two thirds of patients. We saw no benefit of using the intraarterial route to administer cisplatin.     

The oxygen and carbon monoxide reactions of heme oxygenase

The O2 and CO reactions with the heme, alpha-hydroxyheme, and verdoheme complexes of heme oxygenase have been studied. The heme complexes of heme oxygenase isoforms-1 and -2 have similar O2 and CO binding properties. The O2 affinities are very high, KO2 = 30-80 microM-1, which is 30-90-fold greater than those of mammalian myoglobins. The O2 association rate constants are similar to those for myoglobins (kO2' = 7-20 microM-1 s-1), whereas the O2 dissociation rates are remarkably slow (kO2 = 0.25 s-1), implying the presence of very favorable interactions between bound O2 and protein residues in the heme pocket. The CO affinities estimated for both isoforms are only 1-6-fold higher than the corresponding O2 affinities. Thus, heme oxygenase discriminates much more strongly against CO binding than either myoglobin or hemoglobin. The CO binding reactions with the ferrous alpha-hydroxyheme complex are similar to those of the protoheme complex, and hydroxylation at the alpha-meso position does not appear to affect the reactivity of the iron atom. In contrast, the CO affinities of the verdoheme complexes are >10,000 times weaker than those of the heme complexes because of a 100-fold slower association rate constant (kCO' approximately 0. 004 microM-1 s-1) and a 300-fold greater dissociation rate constant (kCO approximately 3 s-1) compared with the corresponding rate constants of the protoheme and alpha-hydroxyheme complexes. The positive charge on the verdoporphyrin ring causes a large decrease in reactivity of the iron.