A mitogenic peptide amide encoded within the E peptide domain of the insulin-like growth factor IB prohormone.

We have identified an amino acid sequence within the E peptide of the insulin-like growth factor IB (IGF-IB) precursor that is biologically active and designated this peptide insulin-like growth factor IB-(103-124) E1 amide (IBE1). Its existence was predicted by a flanking Gly-Lys-Lys-Lys, a signal sequence for sequential proteolytic cleavage and peptidyl C-terminal amidation. A synthetic analog of the predicted IBE1 peptide, designated Y-23-R-NH2, was generated with tyrosine added at position 0.

Chromosome abnormalities in human non-small cell lung cancer.

Clonal cytogenetic abnormalities found in 30 non-small cell lung carcinomas (NSCLC), including 28 newly diagnosed primary tumor specimens, are summarized. Multiple chromosome alterations were identified in every case, and 19 of 30 tumors had near-triploid or near-tetraploid karyotypes. Polysomy 7 and partial gains of 7p, including 7p11-p13 (site of the EGFR gene), were particularly frequent, occurring alone or in combination in 26 tumors.

Early events in the neoplastic transformation of respiratory epithelium.

The complex process of epithelial carcinogenesis is composed of discrete biologic events including the early activation events of "initiation" and "promotion." For lung cancer, these events are only now being elucidated. Despite the identification of possible target genes and their mutations, the "initiation" events for lung cancer remain poorly understood.

Alpha-amidation of peptide hormones in lung cancer.

Small-cell lung cancer (SCLC), the most common neuroendocrine tumor in humans, provides an excellent model system for analyzing the role of growth factors in lung cancer. SCLCs secrete a wide range of peptide hormones, including some that stimulate tumor cell growth, such as gastrin-releasing peptide and insulin-like growth factor I. Many of these peptides are synthesized as prohormones that acquire biological activity only after specific post-translational modifications.

Correlation of model chromosome number of cultured non-small cell lung carcinomas with DNA index of solid tumor tissue.

The modal chromosome number of 13 non-small cell lung carcinomas placed into culture was compared to the DNA index of the tumor tissue as measured by flow cytometry in order to determine whether cytogenetic results from such cultures are representative of the original solid tumor. The modal chromosome number observed in culture, which ranged from 45-146, fell within the range of aneuploidy predicted from the DNA content of the original tissue in all 13 cases. In 7 cases, flow cytometry results showed that the aneuploid G1/G0 population of the tumor tissue (DNA index of 1.

Thalamic stimulation for the treatment of tremor and other movement disorders.

Thalamic stimulation for the treatment of tremor and other motor movement disorders is attractive in view of the fact that it is a non-destructive procedure. With the experience of 26 cases indications can be defined. The method is an alternative for treatment of tremor only when thalamotomy carries a high risk of complications.

Chromosome alterations in 21 non-small cell lung carcinomas.

Cytogenetic analysis was performed on 16 primary tumors, 2 effusions, and 3 cell lines from 21 patients with non-small cell lung cancer (NSCLC). In 20 patients specimens were obtained prior to initiating cytotoxic therapy. Extensive clonal chromosome alterations were found in all cases.

Induction of micronuclei in cultured human bronchial epithelial cells by direct-acting carcinogens.

The sensitivity of human bronchial epithelial cells to induction of micronuclei was determined in cultures derived from seven different donors. Two direct-acting carcinogens, dl-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and N-methyl-N'-nitro-N-nitrosoguanidine were used to induce micronuclei. Both agents increased the incidence of micronuclei in a concentration-dependent fashion in cells from most donors, event at concentrations that did not produce appreciable cytotoxicity; there were considerable variations in the responses of different donors.

Transfection of cytochrome P450 cDNAs into mammalian cells used in mutation and transformation assays.

The present work demonstrates that cDNAs coding for cytochrome P450 enzymes can be transfected into mammalian cells and expressed. In the present studies, two different cell systems were used for transfection: 10T1/2 cells which can be used to study initiation and promotion (Diamond, 1984) and AHH-1 cells which can be used to study mutation and clastogenesis (Crespi and Thilly, 1984, Crespi and Penman, 1989). Thus, a diversity of endpoints can be studied in cells which have increased metabolic capability.

[Palliative neurosurgical treatment of chronic pain following peripheral nerve lesions].

Pathogenesis of pain after traumatic or iatrogenic lesions to peripheral nerves as well as local and conservative therapeutic possibilities are briefly reviewed. If pain subsides or in the case of relapse with establishment of a chronic pain-state the therapy of choice consists in implanting a programmable neuro-stimulator with the electrodes placed near the dorsal sensory roots in the cervical epidural space for the upper extremities or along the posterior columns of the medulla in the thoracic epidural space for the legs. With a success rate for long term pain control of approximately 80% this reversible method which is well tolerated by the nervous system should always be considered for deafferentation-pain (neurogenic pain).

Culture of primary lung tumors using medium conditioned by a lung carcinoma cell line.

Medium conditioned by the established lung tumor cell line A549 was used as a supplement to culture cells from primary solid lung tumors. Of 36 cases placed into culture, primary cells were obtained in 33 (91.7%).

[Neurosurgical indications in the treatment of chronic pain].

Better knowledge in the transmission of pain signals, clinical analysis of pain allowing its aetiopathogenic interpretation (neurogenic pain, somatogenic pain), and technical improvements in neurosurgical interventions that have now become non-traumatic, increasingly selective with less and less general anaesthesia and without prolonged hospitalization, most often allowing precise postoperative control of the intervention, have given neurosurgery a fresh impetus and a major place in the multidisciplinary therapeutic approach to chronic pain. From being exclusively destructive, the neurosurgery of chronic pain has acquired a resolutely conservative orientation with a neurophysiological approach (therapeutic neurostimulation methods) as well as a broader range via a biochemical approach (drug application in the vicinity of neuromediator receptors).

Transfection of a rat cytochrome P450b cDNA into C3H10T1/2CL8 mouse embryo fibroblasts.

A cDNA clone of a rat cytochrome P450b gene was used to construct an expression vector driven by an SV40 promoter and containing a G418-resistance selectable marker. This bifunctional plasmid (pJRSL100) was transfected into the C3H 10T1/2CL8 mouse embryo fibroblast cell line. G418-resistant clones were selected and tested for enhanced sensitivity to the carcinogen 2-acetylaminofluorene (2-AAF), a compound that does not normally induce cytotoxicity or morphological transformation in these cells.

Response of primary human lung carcinomas to autocrine growth factors produced by a lung carcinoma cell line.

Medium conditioned for 48 to 72 h by A549-1 lung carcinoma cells was used to culture primary solid lung tumors on feeder layers of inactivated Swiss 3T3 cells. Of 22 cases placed into culture, primary cultures of carcinoma cells were obtained in 20. Subcultures were obtained in 18 cases, and cell lines were established in nine cases.

Carpal tunnel syndrome in dialysis patients: comparison between continuous ambulatory peritoneal dialysis and hemodialysis populations.

Carpal tunnel syndrome (CTS) has been reported with increased frequency in hemodialysis (HD) patients. A comparative study of patients on continuous ambulatory peritoneal dialysis (CAPD) has not been previously reported. To delineate the significance of dialytic modality and access-related risk factors, this study investigated the incidence and patient characteristics of CTS in CAPD v HD populations.

Electrostimulation and neurosurgical measures in cancer pain.

Neurosurgery for cancer pain may always be considered when the pain no longer responds to conservative treatment methods or only at the cost of undesirable side-effects. Almost all these operations that can be considered for the cancer patient can be performed percutaneously, without general anaesthesia, without loss of blood, and with short hospitalization. Chronic pain has to be differentiated according to whether it is somatogenic or neurogenic.

Intrathecal application of drugs for muscle hypertonia.

The literature regarding the intrathecal use of morphine, baclofen, and midazolam to treat spasticity is reviewed. Nine patients with significant spasticity due to different etiologies were treated. Morphine and midazolam decreased spasticity but did not change the patient's functional status.

Genes for tumor markers are clustered with cellular proto-oncogenes on human chromosomes.

We have analyzed the relative mapping positions of genes for polypeptides expressed abnormally in tumors (tumor markers) and cellular proto-oncogenes and find a remarkable degree of co-mapping of tumor marker genes with oncogenes in the human karyotype. We propose that aberrant expression of marker genes in tumors may be related to their proximity in the human genome to oncogenes expressed during the development of malignancy, and we suggest ways to test this hypothesis of concerted abnormal gene expression in mammalian tumor cells.