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The usefulness of rare neutral gene polymorphisms as an HLA haplotype marker and as a probe for founder effect in small populations was tested by determining the frequency and MHC associations of an NcoI polymorphism in the P450c21 genes in the Finnish population. In the general population, 13% (9 of 70) of samples had the NcoI site. A very strong association with the HLA-B62, Bf*F, C4A*3, C4B*Q0, DRB1*13, DQA1*0103, DQB1*0603 alleles was observed. P450c21A and P450c21B gene-specific amplifications mapped the polymorphic site to both P450c21A pseudogene and P450c21B functional gene of this haplotype in all cases. The majority of haplotypes with the NcoI cutting site found in this population may thus have derived from a single ancestral haplotype. The HLA homozygous cell lines with the NcoI site showed heterogeneous HLA associations. Our results suggest that in small populations the variety of MHC haplotypes may be surprisingly low and rare polymorphisms can serve as informative markers.

We describe a 47-year-old man who had rapidly progressive heart failure caused by giant cell myocarditis with no response to steroid therapy. A successful heart transplantation was performed after life-threatening arrhythmias. The diagnosis was made by endomyocardial biopsy before transplantation, and it was confirmed by the histologic condition of the recipient heart. The patient has been on a triple-immunosuppression therapy with no signs of rejection or recurrence of giant cell myocarditis 23 months after surgery.

Angiogenesis, the process by which new blood vessels are formed, is essential in reproduction, development, wound repair and oncogenesis. Endothelial receptor tyrosine kinases are likely to play key roles in the intercellular signalling controlling angiogenesis. We have here analysed the expression of the endothelial receptor tyrosine kinase tie during the earliest stages of vascular development. The mouse tie cDNA was isolated and sequenced and the exon structure of the coding region was determined. The part of the tie gene encoding the extracellular domain was found to be organized in exons specifying the characteristic domains of the Tie polypeptide. Early postimplantation mouse tissues were analysed for tie expression by in situ hybridization. No tie mRNA was detected in 7.5 day mouse embryos. In 8.5 day embryos, tie expression was observed in differentiating angioblasts of the head mesenchyme, in the splanchnopleure and dorsal aorta as well as in migrating endothelial cells of the developing heart. A weak tie signal was also obtained from angioblasts in the blood islands of the yolk sac. Furthermore, tie mRNA was prominent in the endocardium of the embryo and in the endothelial cells forming the lung vasculature. Expression of tie persisted in the lung capillaries of adult mice, but was decreased in the endocardium. These results suggest that the tie receptor tyrosine kinase is involved in angiogenesis and/or maintenance of endothelial cell functions.

The risk of brachial plexus injury as a complication of coronary bypass operation should be emphasized since the number of coronary operations is rapidly increasing. We describe six patients who developed symptoms consistent with brachial plexus injury after coronary bypass surgery. Four out of six patients had definitive electroneuromyography (ENMG) abnormalities consistent with an acute injury in the brachial plexus. Abnormal somatosensory evoked potential (SEP) was seen in two patients studied. Two of our patients suffered from diabetic polyneuropathy, which even seems a predisposing factor for plexus brachialis injury and to prolong the duration of disability. Based on literature and our own experience we strongly recommend the use of ENMG and SEP to all patients who have any postoperative neurogenic symptoms in the upper extremities. These methods confirm the site of the nerve damage, e.g., differentiate brachial plexus injury from peripheral ulnar nerve lesion, and help to predict the outcome.

We have analyzed the regulation of fibroblast growth factor receptors (FGFRs) during retinoic acid (RA) induced differentiation of Tera-2 human embryonal carcinoma cells. Undifferentiated Tera-2 cells expressed mRNAs for all four known FGFRs. Their differentiation led to loss of FGFR-4 mRNA expression and mRNA levels for FGFR-2 and FGFR-3 were considerably downregulated, whereas the mRNA levels for FGFR-1 remained unaltered. A substantial decrease in binding of K-FGF was found to occur upon RA-induced differentiation of the cells. In undifferentiated Tera-2 cells FGF stimulation caused an increase of c-fos mRNA, and c-jun mRNAs, but no increase of junB mRNA, whereas in the differentiated cells, FGFs strongly stimulated the expression of all three genes. Thus differentiation of the Tera-2 cells leads to marked changes in FGFR gene expression as well as to complex alterations in their responses to exogenous FGFs.

Forty patients aged 2 to 5 years who were admitted for paediatric operations were randomly assigned to have either spinal or general anaesthesia. Spinal anaesthesia was achieved with isobaric bupivacaine 0.5% at a dose of 0.5 mg/kg. General anaesthesia was induced with thiopentone 2-5 mg/kg and continued with low-dose fentanyl (1-2 micrograms/kg, oxygen/nitrous oxide/isoflurane (30/70/0.1-0.5%), vecuronium normoventilating the patients. The time spent in the operation room was shorter in the spinal anaesthesia group because the children were awake and could immediately be transferred. The haemodynamic pattern and respiratory function were stable during spinal anaesthesia. After general anaesthesia, respiratory function deteriorated as indicated by arterial desaturation (90%), which was detected in 11 of the 20 patients after general anaesthesia. Vomiting (2), sore throat (4) and micturition difficulties (2) were the adverse events associated with general anaesthesia. Three patients were restless after spinal anaesthesia. It can be concluded that spinal anaesthesia is a suitable anaesthetic technique for paediatric surgery.

We have previously reported the isolation of human FGFR-4 cDNA encoding a receptor for aFGF and shown that the expression patterns of FGFR-1 through FGFR-4 mRNAs are overlapping, but distinct in human fetal tissues (Partanen et al., 1991). In order to define cells and tissues expressing FGFR-4 more accurately, we have cloned mouse FGFR-4 cDNA and used it in Northern and in situ hybridization of mouse embryonic tissues. Our results show that the 3.5 kb FGFR-4 mRNA is expressed in day 10 to full term embryos and newborn mice, with maximal expression levels during days 14-16 p.c. Adult mice express the FGFR-4 mRNA predominantly in the liver, kidney and lung. In in situ hybridization of 10-13 day p.c. mouse embryos, FGFR-4 mRNA is present primarily in tissues of mesodermal origin and in the developing lung and gut. Particularly the mesenchymal tissue in association with the first pharyngeal arch and along the prevertebrae (in developing myotomes) which will differentiate into muscle tissue express high amounts of FGFR-4 mRNA. In addition, the developing metanephros contains FGFR-4 transcripts. These results suggest that FGFR-4 may be particularly important for the differentiation of skeletal muscle and endodermally derived organs.

We have previously cloned from K562 leukemia cells two novel fibroblast growth factor receptors (FGFR-3 and FGFR-4; J. Partanen et al., EMBO J., 10: 1347-1354, 1991). Here we have analyzed the mRNA expression of four different FGFRs, including the two novel genes in human leukemia cell lines. We show FGFR-1, FGFR-3, and FGFR-4 mRNAs in several leukemia cell lines at levels similar to those in solid tumor cell lines. Ligand cross-linking experiments indicate that K562 cells have receptors binding acidic FGF but not basic FGF. Expression of FGFRs in leukemia cells may reflect their presence on normal hematopoietic precursor cells or induction during leukemogenesis or cell culture.

The vascular element of a mixed type of rejection after orthotopic heart transplantation did not respond to steroid therapy in a 30-year-old man. Plasmapheresis was associated with the resolution of the clinical signs of rejection and the microscopic changes of vasculitis in the biopsy specimen. This case suggests that plasmapheresis may be useful in the treatment of acute vascular rejection in heart transplantation.

The receptors for at least two hematopoietic growth factors, namely the stem cell factor and colony-stimulating factor 1, belong to class III receptor tyrosine kinases. Here we describe cloning of a partial complementary DNA for FLT4, an additional member of this gene family from human leukemia cells. The FLT4 tyrosine kinase domain is 79% homologous with the previously cloned FLT1 (M. Shibuya et al., Oncogene, 5: 519-524, 1990) tyrosine kinase and maps to the chromosomal region 5q33-qter. We have found FLT4 expression in human placenta, lung, heart, and kidney, whereas the pancreas and brain appeared to contain very little if any FLT4 RNA. The results suggest that FLT4 functions in multiple adult tissues.

Although beta-blockers have held their own as the cornerstones of cardiological treatment for almost twenty years, the beneficial effects of these classic agents are not always appreciated in clinical work. Simplified hypertensive treatment or other factors may sometimes argue for the use of newer medicines, but many pathophysiological manifestations of high blood pressure are still best controlled with beta-blockers. The range of available preparations has increased and new compounds are continually appearing on the market.

The functioning of low back muscles of back pain patients during flexion and reextension has not been properly investigated. In this study, we analyzed rectified, averaged electric activity (RMS EMG) and corresponding raw intramuscular (IM) EMG from lumbar paraspinal muscles to quantify the activity level during simple bending cycles in 87 back pain patients compared to 25 able-bodied controls.All functional phases seen in raw IM EMG were also shown in surface RMS EMG. Surface RMS EMG pattern seems to yield more information from activity level than IM EMG pattern. The RMS EMG patterns of back pain patients differed from those of controls as follows: (1) There was clearly noticeable activity during standing in back pain patients. (2) There was only a partial decrease of EMG activity after flexion in back pain patients with current pain. (3) The ratio of mean reached at maximal activity level during extension and flexion was less in patients (1.8, SD = 0.5, p less than .001) than able-bodied controls (3.2, SD = 0.8). (4) Segmental differences were observed in IM EMG activities in patients having hypermobility in bending x-ray. (5) Large peak potentials occurred during movements in patients having segmental hypermobility. THE RESULTS indicate that averaged surface recording is a valuable tool in the investigation of dynamic spine functions in back pain patients.

A 47-year-old man with apical hypertrophic cardiomyopathy and an apical left ventricular aneurysm with palpitation as the initial manifestation is described. There was no intraventricular pressure gradient. The aneurysm is suggested to be a part of the myocardial disease or to be caused by myocardial bridging of the left anterior descending coronary artery demonstrated by angiography. The 24-hour ambulatory ECG recording showed only isolated ventricular ectopic beats and the clinical course has been favorable during 20 months without therapy.

We have isolated a cDNA encoding a novel tyrosine kinase family member, named cyl (consensus tyrosine-lacking kinase), from the K562 human leukemia cell line. The deduced cyl protein lacks signal and transmembrane sequences but contains features of known cytoplasmic tyrosine kinases, including amino-terminal SH3 and SH2 domains. However, having very short amino and carboxy termini, cyl does not seem to belong to any of the previously characterized subfamilies of cytoplasmic tyrosine kinases. Furthermore, cyl lacks the highly conserved tyrosine autophosphorylation site (Y416src) in the tyrosine kinase catalytic domain. The cyl gene is located on human chromosome 15. It is expressed ubiquitously as two independently regulated mRNA species of 2.6 and 3.4 kb in human leukemia cell lines and fetal tissues.

Electroneurophysiological abnormalities have been reported in some patients with dementia, but the data available is rather limited and controversial. We studied nerve conduction velocities and electromyography in 59 patients with moderate to severe involvement of Alzheimer's disease. Except some occasional mono- and polyneuropathies, the patients showed no systemic dysfunction of the peripheral nervous system.

The preoperative diagnostic accuracy of electroneuromyography and myelography was evaluated in 77 patients with cervical radiculopathy and/or myelopathy. In 57% of the patients, the affected root level could be determined with ENMG (accuracy 1-2 segments), 10% had a non-specific finding, and in 33% of the patients, ENMG was normal. If the symptoms had lasted less than three months, 67% of the patients had a localizing finding in ENMG. Among the 97 operated root levels, there were distinct findings in myelography in 79, minor root sheath deformities in 13, and the finding was negative in five. In addition, in myelography there were clearly pathological root sheath deformities at 20 and minor changes at 20 root levels which were not operated. ENMG and myelography have a complementary role in the diagnosis of cervical root compression. By combining the information of ENMG and myelography, the functional significance of the morphological root sheath deformities can be assessed.

In a Finnish family covering four generations many members had immunological symptoms or disorders (mostly skin or joint oriented) with the presence of the B8 antigen positive Major Histocompatibility Complex (MHC) haplotype. Immunological parameters including the presence of autoantibodies, quantitative analysis of the complement components C4, Factor B (BF) and C3 and the serum capacity to inhibit immune precipitation were investigated in relation to the genetic MHC markers. The results showed the importance of the high frequency of the C4A null alleles to these disorders.

Low back pain patients (N = 18) having segmental hypermobility in one lumbar segment and healthy controls (N = 13) were chosen for this study. Patients had no other structural spinal pathology except displacement of one vertebra to another in lateral X-ray bending pictures. Kinetic intramuscular EMG-activity from paraspinal muscles was studied off-line during back flexion and reextension. Routine needle EMG study of paraspinal muscles was also performed in addition to measurements of the tibial nerve H-reflexes and peroneal F-responses. Results showed that the number of MUAPs in erector spinae muscle on voluntary efforts was rarefied at hypermobile levels, and spontaneous activity, positive sharp waves and high frequency discharges were found in more than half of the patients in paraspinal muscles, usually at hypermobile levels only. No signs of proximal nerve root compression were found. This indicates neuropathy of dorsal rami at the instable level.

The integration of distribution network information and remote control systems is discussed. The combined system can incorporate many new applications for the supervision of distribution networks. For example, the management of the actual switching state of networks including real time load flow calculations and an automated fault diagnosis expert system can be implemented when combining data from the network information and SCADA systems. The paper gives a general description of the integrated system and the main features of new applications for network control.

To study the relationship between cholinergic pathology and EEG deterioriation, spectral EEG and CSF neurotransmitter markers were examined in 23 probable AD patients. CSF acetylcholinesterase was correlated with delta power and alpha/delta ratio. In an autopsy study, cortical ChAT activity and the nucleus basalis cell number were lower and delta power higher in 4 demented patients than in 6 age-matched controls. In the group of demented patients, the lowest ChAT activities were associated with the highest delta power.