Biomedical subjects

R Lindberg

Publications and source records attributed to R Lindberg.

At least 19 recordsLinked to original sources

PubMed1995

Immunoreactivity of the central nervous system in cats with a Borna disease-like meningoencephalomyelitis (staggering disease).

The inflammatory cell composition and the expression of major histocompatibility complex (MHC) antigens in the central nervous system (CNS) of 13 cats with a spontaneous, Borna disease-like meningoencephalomyelitis (staggering disease) was investigated by immunohistochemistry with a panel of monoclonal and polyclonal antibodies. T lymphocytes were the predominating inflammatory cells within the adventitial space. CD4+ T cells were more abundant than CD8+ T cells. Scattered IgG-, IgA- and IgM-containing cells were found in the adventitial space and surrounding neuropil, often adjacent to neurons. There was a markedly increased MHC class II expression in cells morphologically resembling microglia. In several cats, Borna disease virus specific antigen was detected, but only in a few cells, mainly of macrophage character. Our findings indicate a long-standing inflammatory reaction in the CNS of cats with staggering disease, possibly triggered and sustained by a persistent viral infection.

Animals↗

PubMed1995

Acquired resistance against Schistosoma bovis after single or repeated low-level primary infections in goats.

Experimental Schistosoma bovis infections were studied in groups of six goats for 32 weeks. Two types of primary infections, a single exposure to 400 cercariae per goat or repeated (trickle) exposure to 200 cercariae per goat weekly for 10 weeks, were followed by a challenge infection with 2000 cercariae per goat in week 16 of the experiment. Periods of high faecal egg excretion were associated with reduced weight gain, anaemia, hypoalbuminaemia and blood eosinophilia; these changes gradually diminished with decreasing faecal egg excretion but never disappeared completely. The pathogenic effects of the trickle exposure exceeded those of the single primary exposure. After the challenge, the goats excreted few or no additional eggs and no additional clinicopathological changes were observed in the group previously exposed to a trickle infection. However, the primary single infection did not provide full protection against the effects of the challenge infection.

Animals↗

PubMed1995

Tissue response of goats to single or repeated low-level doses and to a massive challenge dose of Schistosoma bovis.

The inflammatory tissue response to Schistosoma bovis in the small intestine and liver of goats was studied by light microscopy 32 weeks after they had been exposed to 10 weekly ('trickle') doses of 200 cercariae or to a single dose of 400 cercariae, and 32 weeks after the same dosing schedules followed by a challenge exposure to 2000 cercariae in week 16 of the experiment, and 16 weeks after a single exposure to 2000 cercariae in week 16 (challenge control). The tissue egg counts in the small intestine were highest in the challenge control group and comparable in the other groups, and corresponded well with the numbers of inflammatory foci per histological section of gut wall. The tissue egg counts in the liver were also highest in the challenge control group, but diffuse hepatic portal fibrosis was more pronounced in the groups with a primary exposure followed by a challenge. The intestinal pathology was compatible with a smaller component of vigorous and acute inflammatory reactions to the eggs in the older than in the more recent infections. The magnitude and morphological characteristics of the inflammatory tissue response did not differ markedly between the goats exposed to the trickle infections and the single doses, and they were not substantially affected by the challenge infection.

Analysis of Variance↗

PubMed1995

Staggering disease in cats: isolation and characterization of the feline Borna disease virus.

A Borna disease virus (BDV)-like agent was isolated from the central nervous system (CNS) of cats with a spontaneous non-suppurative encephalomyelitis ('staggering disease'). In contrast to the rabbit-adapted BDV strain V, which can be propagated in several primary and permanent cell cultures, the cat virus grew only in embryonic mink brain cells. Infection of adult Wistar rats with feline brain tissue material did not result in clinical disease during a period of 5 months, nor in growth of infectious virus in the brain. However, using the brain suspension of a newborn rat inoculated with feline brain tissue material, it was possible to induce typical Borna disease (BD) in four adult rats. This indicates a possible adaptation of the cat virus during passages in rats. By the use of an RT-PCR technique, BDV-specific RNA could be detected in a majority of brain samples from diseased cats. BDV-specific antigen was demonstrated in feline CNS samples both by immunohistochemistry and ELISA. However, the amount of BDV RNA and BDV antigen was less in the cats as compared to horses with BD, providing further support for the notion that a distinct feline BDV strain exists.

Animals↗

PubMed1995

Use of magnetic resonance imaging in central nervous system tumors.

MRI provides additional information about tumor location, extent, and margins. MRI was used in 158 patients with CNS tumors for treatment planning from 1985-89 and they were studied in a prospective manner. The most common site was cerebrum (73 pts), then extradural spinal axis (21 pts) posterior fossa (17 pts), brain stem (14 pts) and pituitary (13 pts), etc. The most common histological primary tumor was glioblastoma multiform (25 pts), then low grade astrocytoma (22 pts), anaplastic astrocytoma (14 pts), pituitary tumor (13 pts), medulloblastoma (9 pts), ependymoma (7 pts), and germ cell tumors (6 pts). Twenty-nine patients had metastasis to the brain. A majority of the patients with CNS tumors had the studies using Gadolinium-DTPA. Of the patients with CNS tumors, 120 (76%) had better information based on the MRI, which improved the treatment planning (using the three dimensional images) and field arrangement. In 89 patients (56%) the MRI was very decisive in the treatment volume and field arrangement. In 31 patients (20%) the MRI was beneficial and confirmed the treatment plan. MRI provides important additional information for radiation therapy planning.

Central Nervous System Neoplasms↗

PubMed1991

Alteration of high and low spin equilibrium by a single mutation of amino acid 209 in mouse cytochromes P450.

The identities of the amino acid at position 209 are most critical in determining specific coumarin 7- and steroid 15 alpha-hydroxylase activity in P450coh and P450(15)alpha, respectively. This system, therefore, provides us with an excellent model to study the structural basis for P450 specificity as a monooxygenase. We expressed in Saccharomyces cerevisiae a series of the mutated P450s in which residue 209 was substituted with the various amino acids and characterized the spectral property and hydroxylase activity of these mutated P450s. The positioning of a hydrophobic residue including Phe, Leu, and Val at position 209 resulted in shifting the P450 to the high-spin state, while a charged amino acid such as Lys or Asp produced the low-spin form. Moreover, a P450 with Asn or Gly in this position exhibited spectra indicating a mixture of the high- and low-spin forms. This spin alteration, depending upon the hydrophobicity and size of residue at position 209, indicates that this position is likely to reside close to the sixth axial ligand on the distal surface of the heme in these P450s. This proximity of residue 209 to the ligand may explain the critical role of this residue in determining the hydroxylase specificity and activity of these P450s.

Amino Acids↗

PubMed1991

Pulmonary gas exchange correlated to clinical signs and lung pathology in horses with chronic bronchiolitis.

Eight horses (mean weight 438 kg) with chronic obstructive pulmonary disease (COPD) were studied for clinical signs, ventilation/perfusion relationships (VA/Q) and lung morphology. Four horses were killed and necropsied after the study. In horses with COPD, minute ventilation was almost twice as high as normal, whereas PaO2 was significantly decreased. Cardiac output was normal, but pulmonary artery pressure and pulmonary vascular resistance were significantly increased. The VA/Q distribution was abnormal with an increased scatter of VA/Q ratios. However, shunt (VA/Q = 0) was increased in one horse only. Ventilation of dead space and high VA/Q regions (VA/Q greater than 10) were increased markedly and comprised 74 per cent of minute ventilation. On lung biopsy, all horses showed chronic bronchiolitis with epithelial hyperplasia and metaplasia. Diffuse acinar hyperinflation also was evident at necropsy. There was a significant inverse correlation between the respiratory rate and the fractional ventilation of normal VA/Q regions. Also, there was a significant agreement between the extent of bronchiolar epithelial hyperplasia in necropsy specimens of lungs and the degree of ventilation of high VA/Q regions and dead space. The findings suggest that hyperinflation of the lung due to obstructed airways may be the common denominator of increased ventilation of high VA/Q regions and dead space ventilation and of elevated pulmonary artery pressure in horses with COPD from chronic bronchiolitis.

Animals↗

PubMed1991

Percutaneous gastrostomy. A clinical and experimental study.

Fluoroscopic percutaneous gastrostomy for the purpose of nutrition was performed in 28 patients with the aid of a specially designed gastrostomy set. No major complications were reported. Exchange to Foley catheter was performed after 7 days and could be used without complications for the patients' remaining life span. In order to evaluate the formation of a gastrocutaneous tract, an experimental study with the same instruments as in clinical practice was performed in 13 rabbits. Within one week a gastrocutaneous tract was formed, which was possible to dilate for insertion of a balloon catheter of larger size. The described procedure is a simple and time-saving method for a percutaneous gastrostomy in debilitated patients with dysphagia.

Aged↗

PubMed1990

Extradural administration of bupivacaine: pharmacokinetics and metabolism in pregnant and non-pregnant women.

We found a similar time (about 0.4 h) to maximum serum concentration after extradural administration of bupivacaine 1.78 (SD 0.27) mg kg-1 to six pregnant patients at term, 1.58 (0.13) mg kg-1 to six women younger than 65 yr and 1.50 mg kg-1 to six women older than 65 yr. There were no significant differences in terminal half-life. No unconjugated 4'-hydroxy-bupivacaine was detected in the serum and urine of pregnant patients, in contrast with the other groups. The pregnant patients had significantly greater serum concentrations of the N-dealkylated metabolite, N-desbutyl-bupivacaine (DBB), than the non-pregnant groups. In contrast with 4'-hydroxy-bupivacaine, no conjugated forms of bupivacaine and desbutyl-bupivacaine were detected in urine. The mean total urinary excretion of bupivacaine and its metabolites and their conjugates varied between 2.46 and 3.22% of the total dose administered in the three patient groups, indicating that both 4'-hydroxylation and N-dealkylation are minor metabolic pathways in man.

Adult↗

PubMed1990

Characterization and regulation of sex-specific mouse steroid hydroxylase genes.

We characterized the genes of the male-specific mouse steroid 16 alpha-hydroxylase (C-P-45016 alpha) and the female-specific mouse steroid 15 alpha-hydroxylase (P-45015 alpha) within two distinct gene families. In spite of the high structural identities within each family, the expression of the hydroxylase genes is uniquely regulated. Moreover, the other family members encode the P-450s which are structurally very similar to the hydroxylases but are not able to catalyze steroid hydroxylase activities. For example, only a single amino acid substitution creates steroid 15 alpha-hydroxylase activity in another family-member P-450coh, which catalyzes coumarin 7-hydroxylase but little steroid hydroxylase activity. It appears, therefore, that the mouse P-450 gene families evolved through gene duplication and selective mutation to create new P-450s structurally as well as to establish novel regulatory elements for the gene expressions.

Amino Acid Sequence↗

PubMed1989

Mouse steroid 15 alpha-hydroxylase gene family: identification of type II P-450(15)alpha as coumarin 7-hydroxylase.

We identified type II P-450(15)alpha as mouse coumarin 7-hydroxylase (P-450coh). Unlike type I P-450(15)alpha, the other member within the mouse steroid 15 alpha-hydroxylase gene family, type II catalyzed little steroid 15 alpha-hydroxylase activity, yet structurally there were only 11 substitutions between type I and type II P-450(15)alphaS within their 494 amino acid residues (Lindberg et al., 1989), and the N-terminal sequence (21 residues) of P-450coh was identical with that of both P-450(15)alphaS. Induction by pyrazole of coumarin 7-hydroxylase activity correlated well with the increase of type II P-450(15)alpha mRNA in 129/J male and female mice. Pyrazole, on the other hand, was less in males or not effective in females in inducing the 15 alpha-hydroxylase activity and type I P-450(15)alpha mRNA. Expression of type I and II in COS-1 cells revealed that the latter catalyzed coumarin 7-hydroxylase activity at 10 to approximately 14 pmol min-1 (mg of cellular protein)-1. The former, on the other hand, had a high testosterone 15 alpha-hydroxylase but little coumarin 7-hydroxylase activity. It was concluded, therefore, that type II P-450(15)alpha is the mouse coumarin 7-hydroxylase. Identification of type II as the P-450 specific to coumarin 7-hydroxylase activity and characterization of its cDNA and gene, therefore, were significant advances toward understanding the basis of genetic regulation of this activity in mice (known as Coh locus).

Animals↗

PubMed1989

The structure and characterization of type I P-450(15) alpha gene as major steroid 15 alpha-hydroxylase and its comparison with type II P-450(15) alpha gene.

The structures of genes 15 alpha OH-1 and 15 alpha OH-2, within the mouse steroid 15 alpha-hydroxylase (P-450(15) alpha) family were determined. Genes 15 alpha OH-1 and -2 encoded mouse Type I and II P-450(15) alpha, respectively (Squires, E.J., and Negishi, M. (1988) J. Biol. Chem. 263, 4166-4171). The two genes, which spanned approximately 8 kilobase pairs of total length, showed nearly identical structures and were divided into nine exons at the same positions. A high nucleotide sequence homology (greater than 96%) indicated that 15 alpha OH-1 and -2 were duplicated within 5 million years. The two major transcription start sites were located at 14 and 24 base pairs (bp) upstream from the initiation Met in both genes. No tissue-specific difference in 15 alpha OH-1 and -2 transcriptional start sites was found in mouse liver and kidney. Both 15 alpha OH-1 and -2 had TATA and CAAT boxes at 30 and 100 bp, respectively, upstream from their major transcription start sites. A glucocorticoid regulatory element was present at 336 bp upstream from the start site in both genes. In addition to these motifs, 15 alpha OH-2 had an SV40 enhancer core sequence immediately downstream from its CAAT box. There were only 11 substitutions between Type I and II P-450(15) alpha in their 494-amino acid residues. Type I cDNA-transfected cell homogenates had testosterone 15 alpha-hydroxylase activity at approximately 9 pmol/min/mg protein. Type I also catalyzed progesterone and androstenedione 15 alpha-hydroxylase activities. Type II, on the other hand, exhibited little activity toward these steroids. The results indicated that Type I was the major steroid 15 alpha-hydroxylase. The differential 15 alpha OH-1 expression, therefore, determined the sexual dimorphism of the tissue-specific 15 alpha-hydroxylase activity in mice.

Amino Acid Sequence↗

PubMed1989

Prevalence of debrisoquine oxidation phenotypes in glaucoma patients.

The oxidation of debrisoquine, a sympatholytic antihypertensive agent, exhibits genetic polymorphism. The debrisoquine/4-OH-debrisoquine metabolic ratio (MR) separates the population to poor (PM, MR greater than 12.6) and extensive (EM, MR less than 12.6) metabolizers. 5-10% of the caucasians belong to the PM phenotype. The oxidation of many other drugs, like timolol, correlates with the debrisoquine phenotype. We determined the debrisoquine phenotype in 102 glaucoma patients. The majority of the patients was treated with ophthalmic timolol. Five patients were classified as PMs. However, two of them were on quinidine, a well known inhibitor of debrisoquine oxidation. The prevalence of debrisoquine PM phenotype in glaucoma patients was 2.9% (excluding patients on quinidine) or 4.9% (with patients on quinidine). The figures are slightly lower than the mean value reported for the normal Finnish population. However, both figures lay within the 95% confidence limits of the prevalence of PM phenotype in the normal Finnish population. The beta-blocking activity of oral timolol is increased in PMs. The significance of timolol oxidation phenotype during ocular timolol therapy warrants further investigation.

Cross-Sectional Studies↗

PubMed1989

Budd-Chiari syndrome secondary to hepatic vein thrombus from Wilm's tumor. Case report and literature review.

We describe a case of Budd-Chiari Syndrome in a 6-year-old boy secondary to Wilm's tumor. The patient had a right nephrectomy and mediastinotomy with removal of the tumor from the right atrium, inferior vena cava, and hepatic vein. Postoperatively, the patient had chemotherapy consisting of Actinomycin-D to be followed by radiation to the tumor bed to a total dose of 2000 rads in 10 fractions by using AP/PA field on 6 MeV Linear Accelerator. Currently, the child is receiving combination chemotherapy.

Budd-Chiari Syndrome↗

PubMed1988

Treatment of soft tissue sarcomas by preoperative irradiation and conservative surgical resection.

From 1970-1984, 114 patients with soft-tissue sarcomas received preoperative irradiation at U.T.M.D. Anderson Hospital. Two patients refused surgery and two had progressing disease and therefore did not proceed to surgery; in the remaining 110 patients, conservative surgical resections were performed 3-6 weeks following irradiation. Analysis of survival by histologic type, age, primary size, and histologic grade revealed a significant negative correlation with grade 3 and to a lesser extent to primary size greater than 15 cm. Eleven patients failed within the radiation portal for the primary, four in conjunction with distant metastases. Of the remaining seven, four were salvaged by further surgery for an ultimate primary-only failure rate of three. Distant metastasis occurred in 35 patients and was the major mechanism of treatment failure in this experience. Adjunctive chemotherapy was not used for the majority of patients and it remains to be seen if its routine employment in large, high-grade, lesions will diminish the deaths caused by distant metastases.

Adult↗

PubMed1988

Debrisoquine oxidation in a Finnish population: the effect of oral contraceptives on the metabolic ratio.

1. The debrisoquine hydroxylation phenotype was assessed in 211 healthy subjects of Finnish Caucasian origin. 2. A bimodal distribution was observed in the urinary debrisoquine/4-hydroxydebrisoquin ratio. Eleven subjects (about 5%) were poor metabolizers of debrisoquine, when a ratio of 12.6 was used as the cut-off point. 3. The mean metabolic ratio of 35 extensive metabolizers taking oral contraceptives was slightly lower than that of extensive metabolizers not taking contraceptives. This indicates that oral contraceptives may change the phenotyping near the metabolic ratio of 12.6. 4. The metabolic ratios were determined in eight subjects using both 4 h and 6 h urine collection times. The metabolic ratios corresponded well with each other indicating the usefulness of the shorter 4 h collection time.

Adult↗

PubMed1987

Noradrenergic and dopaminergic effects of nomifensine in healthy volunteers.

Intravenous doses (100 mg in 20 minutes) of the antidepressant drug nomifensine, administered to male volunteers, increased heart rate and blood pressure, elevated the plasma levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and powerfully stimulated growth hormone release and inhibited the secretion of prolactin. Oral nomifensine, either as a single 100 mg dose or as a similar dose after 2 weeks' treatment with the drug (150 mg/day), caused none of the above effects. This was in line with the limited (less than 30%) oral bioavailability of the active, unconjugated form of the drug, estimated in the same subjects. MHPG in plasma was slightly but consistently reduced by the 2 weeks' treatment, suggesting reduced turnover of norepinephrine. The observed clinical effects of nomifensine are compatible with uptake inhibition and augmented release of norepinephrine and dopamine and possibly direct agonistic effects on dopamine receptors. Although nomifensine was withdrawn from the market because of immunologic complications, it serves as a model compound of a new pharmacologic class of antidepressants, devoid of many of the disturbing side effects of the tricyclic drugs.

Adult↗

PubMed1987

Reduction of pain at venous cannulation in children with a eutectic mixture of lidocaine and prilocaine (EMLA cream): comparison with placebo cream and no local premedication.

The local analgesic efficacy of a cream formulation of lidocaine and prilocaine (EMLA) in reducing pain at venous cannulation was investigated in children scheduled for elective surgery. Forty children participated in a double-blind, randomized comparison between EMLA and inactive placebo cream. Another group of 18 children without any local treatment was studied as an additional control material. Subjective pain scores, expressed with a visual analogue scale, were significantly lower in the EMLA group compared with both the group treated with placebo cream (P less than 0.001) and the open control group (no cream; P less than 0.01). Local pallor and slight oedema were the only side-effects, registered in both cream-treated groups. A preliminary study was also carried out with 10 children (five with EMLA and five without) in order to determine whether catecholamine and vasopressin levels in venous blood are affected by the stress and anxiety associated with venepuncture in children premedicated with oral flunitrazepam. No significant hormone responses were, however, detected. The lidocaine concentrations measured in venous blood taken from the application site of EMLA cream were low, and there were no measurable levels of lidocaine in simultaneous blood samples from the opposite extremity. In our opinion EMLA cream is safe and alleviates effectively the pain associated with venepuncture, and thus deserves a place in the routine premedication of children.

Administration, Cutaneous↗