Showing papers by "Lund University published in 1990"

Vasoactive peptide release in the extracerebral circulation of humans during migraine headache

Abstract: The innervation of the cranial vessels by the trigeminal nerve, the trigeminovascular system, has recently been the subject of study in view of its possible role in the mediation of some aspects of migraine. Since stimulation of the trigeminal ganglion in humans leads to facial pain and flushing and associated release of powerful neuropeptide vasodilator substances, their local release into the extracerebral circulation of humans was determined in patients who had either common or classic migraine. Venous blood was sampled from both the external jugular and the cubital fossa ipsilateral to the side of headache. Plasma levels of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide were determined using sensitive radioimmunoassays for each peptide, and values for the cubital fossa and external jugular and a control population were compared. A substantial elevation of the calcitonin gene-related peptide level in the external jugular but not the cubital fossa blood was seen in both classic and common migraine. The increase seen in classic migraine was greater than that seen with common migraine. The other peptides measured were unaltered. This finding may have importance in the pathophysiology of migraine.

Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease

Abstract: Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-[18F]fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the "on-off" phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.

Optimal Bird Migration: The Relative Importance of Time, Energy, and Safety

Abstract: “Optimization is the process of minimizing costs or maximizing benefits, or obtaining the best possible compromise between the two. Evolution by natural selection is a process of optimization” (R. McNeill Alexander 1982).

Interleukin-1 receptor antagonist reduces mortality from endotoxin shock.

Abstract: About five out of 1,000 patients admitted to hospital develop bacterial sepsis leading to shock, the mortality rate for which is high despite antibiotic therapy. The infection results in hypotension and poor tissue perfusion, and eventually leads to the failure of several organ systems. Bacterial endotoxin is thought to be the direct cause of shock in Gram-negative sepsis, because it can cause shock in animals, and antibodies against endotoxin prevent Gram-negative shock in animals and in humans. But, the symptoms of septic shock are the result of the actions of host cytokines induced by the endotoxin. The cytokine interleukin-1 has been implicated as an important mediator of septic shock because it can induce tachycardia and hypotension and act synergistically with tumour necrosis factor to cause tissue damage and death. We now report that a specific interleukin-1 receptor antagonist reduces the lethality of endotoxin-induced shock in rabbits, indicating that interleukin-1 does indeed play an important part in endotoxin shock.

Enzymatic activity of prostate-specific antigen and its reactions with extracellular serine proteinase inhibitors.

Abstract: Prostate-specific antigen (PSA) is one of the three most abundant prostatic-secreted proteins in human semen. It is a serine proteinase that, in its primary structure, manifests extensive similarities with that of the Arg-restricted glandular kallikrein-like proteinases. When isolated from semen by the addition of chromatography on aprotinin-Sepharose to a previously described procedure, PSA displayed chymotrypsin-like activity and cleaved semenogelin and the semenogelin-related proteins in a rapid and characteristic pattern, but had no trypsin-like activity. About one third of the purified protein was found to be enzymatically inactive, due to cleavage carboxy-terminal of Lys145. Active PSA formed SDS-stable complexes with alpha 1-antichymotrypsin, alpha 2-macroglobulin-analogue pregnancy zone protein. PSA formed inhibitory complexes with alpha 1-antichymotrypsin at a molar ratio of 1:1, a reaction in which PSA cleaved the inhibitor in a position identical to that reported from the reaction between chymotrypsin and alpha 1-antichymotrypsin. The formation of stable complexes between PSA and alpha 1-antichymotrypsin occurred at a much slower rate than that between chymotrypsin and alpha 1-antichymotrypsin, and at a similar or slightly slower rate than that between PSA and alpha 2-macroglobulin. When added to normal blood plasma in vitro, active PSA formed stable complexes both with alpha 2-macroglobulin and alpha 1-antichymotrypsin. This complex formation may be a crucial determinant of the turnover of active PSA in intercellular fluid or blood plasma in vivo.

Density matrix averaged atomic natural orbital (ANO) basis sets for correlated molecular wave functions

Abstract: Generally contracted basis sets for second row atoms have been constructed using the Atomic Natural Orbital (ANO) approach, with modifications for allowing symmetry breaking and state averaging. The ANOs are constructed by averaging over several atomic states, positive and negative ions, and atoms in an external electric field. The contracted basis sets give virtually identical results as the corresponding uncontracted sets for the atomic properties, which they have been designed to reproduce. The design objective has been to describe the ionization potential, the electron affinity, and the polarizability as accurately as possible. The result is a set of well balanced basis sets for molecular calculations. The starting primitive sets are 17s12p5d4f for the second row atoms Na-Ar. Corresponding ANO basis sets for first row atoms have recently been published.

The restricted active space self-consistent-field method, implemented with a split graph unitary group approach

Abstract: An MCSCF method based on a restricted active space (RAS) type wave function has been implemented. The RAS concept is an extension of the complete active space (CAS) formalism, where the active orbitals are partitioned into three subspaces: RAS1, which contains up to a given maximum number of hole; RAS2, where all possible distributions of electrons are allowed; and RAS3, which contains up to a given maximum number of electrons. A typical example of a RAS wave function is all single, double, etc. excitations with a CAS reference space. Spin-adapted configurations are used as the basis for the MC expansion

Structure and expression of the human cystatin C gene.

Abstract: The structural organization of the gene for the human cysteine-proteinase inhibitor cystatin C was studied. Restriction-endonuclease digests of human genomic DNA hybridized with human cystatin C cDNA and genomic probes produced patterns consistent with a single cystatin C gene and, also, the presence of six closely related sequences in the human genome. A 30 kb restriction map covering the genomic region of the cystatin C gene was constructed. The positions of three polymorphic restriction sites, found at examination of digests of genomic DNA from 79 subjects, were localized in the flanking regions of the gene. The gene was cloned and the nucleotide sequence of a 7.3 kb genomic segment was determined, containing the three exons of the cystatin C structural gene as well as 1.0 kb of 5'-flanking and 2.0 kb of 3'-flanking sequences. Northern-blot experiments revealed that the cystatin C gene is expressed in every human tissue examined, including kidney, liver, pancreas, intestine, stomach, antrum, lung and placenta. The highest cystatin C expression was seen in seminal vesicles. The apparently non-tissue-specific expression of this cysteine-proteinase inhibitor gene is discussed with respect to the structure of its 5'-flanking region, which shares several features with those of housekeeping genes.

A 1,400-year tree-ring record of summer temperatures in Fennoscandia

Abstract: Tree-ring data have been used to reconstruct the mean summer (April-August) temperature of northern Fennoscandia for each year from AD 500 to the present. Summer temperatures have fluctuated markedly on annual, decadal and century timescales. There is little evidence for the existence of a Medieval Warm Epoch, and the Little Ice Age seems to be confined to the relatively short period between 1570 and 1650. This challenges the popular idea that these events were the major climate excursions of the first millennium, occurring synchronously throughout Europe in all seasons. An analysis of past warming trends suggests that any summer warming induced by greenhouse gases may not be detectable in this region until after 2030.

HER-2/neu amplification predicts poor survival in node-positive breast cancer.

Abstract: HER-2/neu protooncogene amplification and protein expression were analyzed with slot blot and Western blot techniques, respectively, in more than 300 invasive primary breast tumors of all stages. Amplification (2- greater than 30 copies) was found in 17% of these tumors and high expression was seen in 19%. There was a striking coincidence between gene amplification and high expression. Tumors associated with many involved axillary lymph nodes or with Stage IV disease were more often HER-2/neu amplified or overexpressed. Furthermore, gene alteration was strongly correlated with the absence of steroid receptors and with larger tumor size. High expression without gene amplification was seen in a minor subset of tumors of less aggressive character. Neither amplification nor overexpression was correlated with disease outcome for patients with negative axillary lymph nodes. For node-positive patients, however, HER-2/neu amplification was a significant predictor of early relapse and death (median follow-up = 45 months), and a similar trend, although not significant, existed for high gene expression. Multivariate analyses indicated that HER-2/neu alterations were not independent predictors of patient outcome.

A survey of cache coherence schemes for multiprocessors

Abstract: Schemes for cache coherence that exhibit various degrees of hardware complexity, ranging from protocols that maintain coherence in hardware, to software policies that prevent the existence of copies of shared, writable data, are surveyed. Some examples of the use of shared data are examined. These examples help point out a number of performance issues. Hardware protocols are considered. It is seen that consistency can be maintained efficiently, although in some cases with considerable hardware complexity, especially for multiprocessors with many processors. Software schemes are investigated as an alternative capable of reducing the hardware cost. >

Sotalol versus quinidine for the maintenance of sinus rhythm after direct current conversion of atrial fibrillation.

Abstract: This open, parallel-group study compares quinidine and sotalol treatment for maintenance of sinus rhythm after direct current conversion of patients with chronic atrial fibrillation. The patients from 15 centers in Sweden were randomized to sotalol (98 patients) or quinidine (85 patients) after 2 hours of sinus rhythm after direct current conversion. According to primary efficacy assessment, 52% of the patients in the sotalol group and 48% of the patients in the quinidine group remained in sinus rhythm during the following 6-month treatment period (NS). Furthermore, 34% of the patients treated with sotalol and 22% of the patients treated with quinidine relapsed into atrial fibrillation (NS). Heart rate after relapsing into atrial fibrillation was higher in the patients treated with quinidine (109 beats/min) than in the patients treated with sotalol (78 beats/min, p less than 0.001). Patients treated with sotalol were found to be less symptomatic at the time of relapse compared with relapsing patients in the quinidine group. In terms of safety, more patients were withdrawn from quinidine than from sotalol treatment (26% vs. 11%, p less than 0.05), and sotalol was generally better tolerated than quinidine. Twenty-eight percent of the patients treated with sotalol and 50% of the patients treated with quinidine reported side effects (p less than 0.01). The difference was primarily a result of early (within the first month of treatment) gastrointestinal and skin side effects in the group of patients treated with quinidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Indicators of prognosis in node-negative breast cancer

Abstract: Measures of the proliferative activity of tumor cells have prognostic value in patients with node-negative breast cancer. We studied 367 women in southern Sweden who had undergone surgical resection for such cancer. Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase). The median duration of follow-up was four years; 28 percent of the patients received adjuvant therapy, usually with tamoxifen (n = 83). A multivariate analysis based on complete data on 250 patients included the following covariates: age (greater than or equal to 75, 50 to 74, and less than or equal to 49 years), tumor size (less than or equal to 20 vs. greater than 20 mm), concentration of estrogen and progesterone receptors (less than 10 vs. greater than or equal to 10 fmol per milligram of protein), ploidy (diploid vs. nondiploid), and S-phase category (fraction of cells in S phase: less than 7.0 percent, 7.0 to 11.9 percent, and greater than or equal to 12 percent). The S-phase fraction yielded the most prognostic information, followed by progesterone-receptor status and tumor size. A prognostic model based on these three variables identified 37 percent of the patients as constituting a high-risk group with a fourfold increased risk of distant recurrence. In the remaining 63 percent of the patients, the five-year overall survival rate (92 +/- 4 [+/- SE] percent) did not differ from the expected age-adjusted rate for Swedish women. We conclude that a prognostic index that includes indicators of the proliferative activity of tumor cells may be able to identify women with node-negative breast cancer in whom the risk of recurrence is sufficiently low that adjuvant chemotherapy can be avoided.

The influence of mild body and brain hypothermia on ischemic brain damage.

Abstract: The influence of brain and body temperature on ischemic brain damage, notably on the density and distribution of selective neuronal vulnerability, was studied in SPF-Wistar rats subjected to 15 min of forebrain ischemia induced by bilateral occlusion of the common carotid arteries combined with arterial hypotension (50 mm Hg) in a room air environment. In one group of animals, the body temperature was maintained at 37°C but no attempt was made to prevent heat losses from the ischemic brain; i.e., the head was not heated during ischemia. Under those conditions the temperature of the caudoputamen and at a subcutaneous site over the skull bone spontaneously fell to ∼32°C. In four other groups, both the rectal and the subcutaneous skull temperatures were maintained at 38, 37, 35, and 33°C during the ischemia. Our results confirm those recently reported when brain temperature was varied during 20 min of ischemia, with body temperature kept constant. Thus, the histopathological outcome of the brain damage, as a...

Cubic phases in surfactant and surfactant-like lipid systems

Abstract: Cubic liquid crystalline phases are common in surfactant and surfactant-like lipid systems at temperatures above the Krafft point. They are optically isotropic and very stiff. Therefore, they are often not recognized as independent phases and separated in pure state. The liquid crystalline nature is evidenced by a low-angle diffraction pattern with sharp reflections having Bragg-values above 20 A coupled with a diffuse wide-angle reflection at 4.5 A, proving that the hydrocarbon moiety is in a liquid state. The cubic phases occur in a variety of lipid/water systems (also with liquid organic solvents), such as simple soaps, amphiphilic lipids of biological origin, and extracts from membrane lipids. The location of the cubic phases in a phase diagram varies. The original concept of a cubic structure composed of closed globular aggregates, either of “oil-in-water” or “water-in-oil” type in face-centered array seems to be obsolete. The present structure concepts include closed anisotropic aggregates, short rod-like aggregates forming continuous networks or lamellar aggregates with “zero” curvature forming networks of Infinite Periodic Minimal Surfaces (IPMS). The structure is mostly primitive or body-centered cubic.

Roentgen stereophotogrammetric analysis.

Abstract: Soon after Roentgen's discovery, the ‘new’ rays were used to produce stereoscopic images or used for spatial reconstruction of positions of foreign bodies. However, no systematic use of roentgen stereo measurements seems to have occurred until the 1970's, although many attempts have been made before. Since 1972, a system for roentgen stereophotogrammetry has been in use at the University Hospital in Lund. The system has been named RSA, roentgen stereophotogrammetric analysis. It is a complete system, including instrumentation for implanting tantalum landmarks, devices for calibration of the stereo roentgen set-up, and comprehensive software. Using different calibration set-ups, any part of the body can be investigated under different conditions using standard roentgen equipment. The computer programs make it possible to calculate spatial landmark coordinates from measured film coordinates, and further to calculate growth, and volume changes or kinematic variables in well-defined and generally used terms. ...

Time-resolved transillumination for medical diagnostics.

Abstract: A time-gated technique to improve the possibility of localizing spatial differences in absorption when transilluminating a turbid, highly scattering medium, such as human tissue, is demonstrated. When transmitting picosecond laser pulses and detecting photons on the opposite side of the object, the contrast can be strongly enhanced by detecting only the photons with the shortest traveling time. Measurements on a 35-mm-thick tissue phantom with 5-mm-diameter absorbing objects inside are reported with data for a human hand in vivo. Implications for optical mammography (diaphanography) are discussed.

The Response of Bean Plants to UV-B Radiation Under Different Irradiances of Background Visible Light

Abstract: Investigations show that UV-B radiation may inhibit photosynthesis in many plants, as well as causing visible leaf symptoms, such as glazing, bronzing, and necrosis. The amount of visible light also plays a role with regard to the extent of UV radiation damage to plants. In the present study using bean, three different irradiances of background visible light were applied together with UV-B radiation in order to test the response of bean to different light levels with regard to anatomical and physiological changes

Reformation of long axon pathways in adult rat central nervous system by human forebrain neuroblasts.

Abstract: THE failure of lesioned axons to regenerate over long distances in the mammalian central nervous system (CNS) is not due to an inability of central neurons to regenerate, but rather to the non-permissive nature of the CNS tissue environment1–4. Regenerating CNS axons, which grow well within a peripheral nerve, for example, fail to penetrate mature CNS tissue by more than about 1 mm1,5,6. Recent evidence indicates that this may be due to inhibitory membrane proteins associated with CNS oligodendrocytes and myelin2–4,7,8. We report here that human telencephalic neuroblasts implanted into the excitotoxically lesioned striatum of adult rats can escape or neutralize this inhibitory influence of the adult CNS environment and extend axons along major myelinated fibre tracts for distances of up to ∼20 mm. The axons were seen to elongate along the paths of the striato-nigral and cortico-spinal tracts to reach the substantia nigra, the pontine nuclei and the cervical spinal cord, which are the normal targets for the striatal and cortical projection neurons likely to be present in these implants.

Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor.

Abstract: Tumor necrosis factor (TNF) is a pleiotropic mediator of inflammatory responses A cysteine-rich, highly glycosylated 30-kD TNF-binding protein (TNF-BP) purified from urine may have a role in regulation because it protects in vitro against the biological effects of TNF The cytotoxic effect of TNF on the fibrosarcoma cell line WEHI 164 was inhibited by 50% at a 10-fold excess of TNF-BP The binding of TNF to the receptor was partially reversed after the addition of TNF-BP Results from biosynthetic labeling of cells with 35S-cysteine followed by immunoprecipitation with anti-TNF-BP indicated that TNF-BP is formed and released at the cell surface by cleavage because no corresponding cellular polypeptide was observed A cellular 60-kD polypeptide, which was immunoprecipitated with anti-TNF-BP, may correspond to the transmembrane TNF-receptor molecule and be the precursor of TNF-BP Thus, TNF-BP appears to be a soluble form of a transmembrane TNF-receptor Moreover our results demonstrate that the production of TNF-BP is increased when the TNF receptor is downregulated in cells by treatment with TNF or by activation of protein kinase C with phorbol esters TNF-BP may be an important agent that blocks harmful effects of TNF, and, therefore, useful in clinical applications

Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study.

Abstract: . The Swedish Ticlopidine Multicentre Study (STIMS) was a double-blind placebo-controlled trial designed to determine whether ticlopidine, a platelet antiaggregatory agent, reduces the incidence of myocardial infarction, stroke and transitory ischaemic attacks in patients with intermittent claudication. A total of 687 patients was monitored for a minimum of 5 years or until an end-point was reached. The number of end points (99 vs. 89), analysed according to the intention-to-treat principle, was 11.4% lower in the ticlopidine group (P = 0.24). The mortality rate was 29.1% lower in the ticlopidine group (64 vs. 89, P = 0.015); this observation could be accounted for by a reduced mortality from ischaemic heart disease. On-treatment analysis showed there to be significantly fewer end points in the ticlopidine group (47 vs. 76, P = 0.017). Diarrhoea was the most common side-effect. Reversible leucopenia or thrombocytopenia was reported in seven patients on ticlopidine. It is concluded that the high morbidity and mortality from cardio- and cerebrovascular disease in patients with intermittent claudication can be reduced by long-term treatment with ticlopidine.

Neuropeptide Y receptor subtypes, Y1 and Y2.

Abstract: Heterogeneity among NPY (and PYY) receptors was first proposed on the basis of studies on sympathetic neuroeffector junctions, where NPY (and PYY) can exert three types of action: 1) a direct (e.g., vasoconstrictor) response; 2) a postjunctional potentiating effect on NE-evoked vasoconstriction; and 3) a prejunctional suppression of stimulated NE release; the two latter phenomena are probably reciprocal, since NE affect NPY mechanisms similarly. It was found that amidated C-terminal NPY (or PYY) fragments, e.g., NPY 13-36, could stimulate selectively prejunctional NPY/PYY receptors, which were termed Y2-receptors. Consequently, the postjunctional receptors which were activated poorly by NPY/PYY fragments, were termed Y1-receptors. Later work has indicated that the Y2-receptor may occur postjunctionally in selected sympathetic effector systems. The central nervous system appears to contain a mixture of Y1- and Y2-receptors as indicated by functional as well as binding studies. For instance, NPY and NPY 13-36 produced diametrically opposite effects on behavioral activity, indicating the action of the parent peptide on two distinct receptors. Cell lines, most importantly neuroblastomas, with exclusive populations of Y1- or Y2-receptors, have been characterized by binding and second messenger studies. In this work, selective agonists for the two receptor subtypes were used. Work of many investigators has formed the basis for subclassifying NPY/PYY effects being mediated by either Y1- or Y2-receptors. A preliminary subclassification based on effects of NPY, PYY, fragments and/or analogs is provided in Table 6. It is, however, to be expected that further receptor heterogeneity will be revealed in the future. It is argued that mast cells possess atypical NPY/PYY receptors. The histamine release associated with stimulation of the latter receptors may, at least in part, underlie the capacity of NPY as well as of short C-terminal fragments to reduce blood pressure. Fragments, such as NPY 22-36, appear to be relatively selective vasodepressor agents because of their weak vasopressor properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Uterine leiomyoma cytogenetics.

Abstract: Uterine leiomyoma--a benign smooth muscle tumor--has recently been found to contain tumor-specific chromosome aberrations. Although only normal karyotypes were detected in 50 to 80% of cytogenetically investigated tumors, 104 leiomyomas with karyotypic aberrations have already been reported. At least four cytogenetically abnormal subgroups have been identified thus far, characterized by rearrangements of 6p, del(7)(q21.2q31.2), +12, and t(12;14)(q14-15;q23-24). The remaining abnormal tumors have had various nonrecurrent anomalies. Secondary karyotypic rearrangements, sometimes including ring chromosomes, have been found in one-third and reflect clonal evolution. Occasional leiomyomas have contained multiple numerical and structural rearrangements. Though benign, these cytogenetically grossly aberrant tumors often displayed more atypical histological features than are usually seen in leiomyoma. Multiple leiomyomas have been investigated from 69 patients, with detection of chromosome anomalies in at least two separate tumors from the same uterus in ten cases. In half of these patients unrelated aberrations were found in different leiomyomas from the same uterus. On other occasions the aberrations were identical, indicating that although some uterine leiomyomas originate independently, others may develop by intra-myometrial spreading from a common neoplastic clone. Some common features are discernible between the karyotypic pictures of uterine leiomyoma and angioleiomyoma; rearrangements of 6p, 13q, and 21q have been described in both tumor types. The cytogenetic similarities so far detected between leiomyoma and the malignant muscle tumors--leiomyosarcoma and rhabdomyosarcoma--are few and may be fortuitous. The cytogenetic profiles of leiomyoma and lipoma are strikingly similar; both tumor types have nonrandom rearrangements of 12q13-15, t(12;14) in leiomyoma and t(3;12) in lipoma, as well as variant rearrangements of the same 12q segment. Both also have cytogenetic subgroups characterized by changes in 6p and ring chromosomes. Finally, karyotypic similarities exists also between leiomyoma and pleomorphic adenoma of the salivary gland, which includes a subset of tumors with anomalies of 12q13-15, and with myxoid liposarcoma, which has t(12;16)(q13;p11) as a tumor-specific rearrangement.