Biomedical subjects

R Lindberg

Publications and source records attributed to R Lindberg.

At least 37 records · Page 2Linked to original sources

PubMed1997

The impact of primary Schistosoma bovis infection on a subsequent challenge infection in goats.

Experimental primary and challenge Schistosoma bovis infections were studied in West African Dwarf goats, using clinicopathological and parasitological parameters. The experiment included 44 goats divided into 4 groups of which group A received primary infection, group B received primary and challenge infection, group C received a challenge control infection, and group D included noninfected controls. Primary infection (wk 0) and challenge infection (wk 16) both comprised exposure to 1,000 cercariae per goat, and necropsies took place 16, 22 and 32 wk following primary infection. Clinicopathological effects were moderate in all infected groups. Egg excretion became gradually reduced following peak levels during early primary infection, and egg excretion increased only marginally following challenge infection in the primary- and challenge-infection group. Similarly, challenge infection of primary-infected goats did not result in an increase in tissue egg counts. Worm recovery and tissue egg counts in primary-infected goats remained comparable throughout the experiment, and although evidence was obtained for a delay in maturation, challenge worm establishment was comparable with challenge-control worm establishment. An anti-fecundity effect is thus an essential component of the regulatory response to both primary and challenge S. bovis infection in the goats. However, it was also shown that the intrauterine egg count is an unreliable parameter for fecundity assessments.

Analysis of Variance↗

PubMed1997

Experimental Schistosoma bovis infection in goats: the inflammatory response in the small intestine and liver in various phases of infection and reinfection.

In a histopathological study of goats experimentally infected with Schistosoma bovis, the characteristics of the inflammatory response in the small intestine and liver related to tissue egg counts and fecal egg excretion were compared between goats at different time periods of primary infection and of primary infection followed by challenge. At early patency, coinciding with increasing egg excretion, the intestinal lamina propria showed numerous intact schistosome eggs devoid of any inflammatory reaction, whereas egg-associated inflammatory foci in the intestine were significantly few. Later in primary infection and after challenge, intestinal changes were marked by a granulomatous anti-egg response, with only a minor component of eggs lacking inflammatory change, and were consistent with a reduction of egg transfer into the gut wall. Hepatocellular necrosis with eosinophil infiltration was pronounced only during the early patent stage. The results indicate that the early cascade of fecal egg excretion in caprine schistosomosis bovis is aided by a low degree of tissue reactivity to eggs in the intestine. They also lend support to previous findings indicating that an anti-fecundity effect is operative after exposure to challenge in this parasitic infection in goats.

Animals↗

PubMed1996

Experimental Schistosoma bovis infection in goats: pathological consequences of praziquantel treatment.

Schistosoma bovis-infected goats were treated with praziquantel (60 mg/kg) and killed for examination 1, 7 or 28 days later. Infected non-treated goats and parasite-free, treated or non-treated goats were included for comparison. The gross pathological changes seen in the infected non-treated groups were mild to moderate. The liver appeared discoloured and moderately enlarged. The intestinal lesions were most prominent in the small intestines, which showed catarrhal inflammation with numerous tiny corpuscles beneath the luminal surface. The mesenteric lymph nodes were slightly to moderately enlarged. In contrast, on macroscopical examination, the infected treated groups invariably showed pronounced liver changes and marked enlargement of the lymph nodes, whereas the lesions in the intestines were comparatively slight. Histological lesions related to dead worms were seen in the livers of all treated animals. These lesions included pronounced inflammatory cellular infiltrates, thrombophlebitis, necrosis and periportal fibrosis, still severe 4 weeks after treatment. In the intestines, the deposition of new eggs with little cellular reaction had almost completely ceased 1 week after treatment. Four weeks after treatment, only a very few egg-associated lesions were noted in the intestines. The presence of severe lesions attributable to dead worms in the liver indicates the need for caution when treating animals with high worm loads or concomitant liver disease.

Animals↗

PubMed1996

Rectal biopsy diagnosis in horses with clinical signs of intestinal disorders: a retrospective study of 116 cases.

The histology from rectal biopsy specimens taken 1980-1990 on 131 occasions from 116 horses, age 1-18 years, with clinical signs of intestinal disease was evaluated and classified retrospectively. In 40 horses, autopsy results were studied for comparison. Biopsy specimens (21 horses) and post mortem rectal tissue (9 horses) from 30 healthy horses, age 4-22 years, were used as controls. In 105 clinical cases, a biopsy was performed on only one occasion, while repeat biopsy was performed in 11 cases. Specimens showed pathological changes in 60 horses. The findings were classified into acute, chronic or chronic active simple proctitis, granulomatous enteritis, eosinophilic granulomatosis/gastroenteritis, eosinophilic proctitis, erosive/ulcerative proctitis, pseudomembranous proctitis, proctitis with vasculitis and malignant lymphoma. Mild scattered neutrophil infiltration in the lamina propria was found in controls, but neutrophils in crypt or surface epithelia were abnormal findings. Depletion or hyperplasia of goblet cells sometimes accompanied inflammation. Simple proctitis occurred in association with malignant lymphoma and various inflammatory disorders of the gastrointestinal tract apparent at autopsy. Eosinophilic granulomatosis/gastroenteritis and granulomatous enteritis were diagnosed from biopsy specimens in 6 of 12 and 4 of 9 cases, respectively, of these diseases confirmed at autopsy. Reduction of acid mucins in goblet cells was a prominent feature of eosinophilic granulomatosis. Rectal biopsy was found to be a useful adjunct for evaluation of intestinal disease in the horse.

Animals↗

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↗

PubMed1994

Pediatric astrocytomas. The Louisville experience: 1978-1988.

PURPOSE: The purpose of this study is to retrospectively analyze all pediatric patients with the diagnosis of astrocytoma treated either definitively or postoperatively in our department from 1978 through 1988. Grade, age, T-stage, tumor location, and extent of resection are individually analyzed as prognostic indicators of overall survival. MATERIALS AND METHODS: Pediatric astrocytoma patients (grades I-IV) diagnosed by CT-guided biopsy or surgical resection were assessed. Patients were treated with external beam radiotherapy to involved fields using 4- or 6-MV photons. Daily doses ranged from 1.5 to 2.0 Gy; total doses from 41.4 to 66 Gy. Treatment was given to 17 patients (9 male, 8 female), aged 18 years and younger: 11 patients had low-grade (I & II) astrocytoma with incomplete margins; 3 patients had anaplastic astrocytoma; and 3 patients had glioblastoma multiforme. RESULTS: Overall survival at 140 months was 63%. Median follow-up of patients living NED was 69 months, with a range of 39-140 months. Nine of the eleven (82%) low-grade patients survived NED; 1 of 3 anaplastic patients is NED at 44 months follow-up; 1 died of intercurrent disease at 80 months; the third died of disease at 49 months. All three glioblastomas succumbed to local disease at 9, 15, and 27 months from diagnosis. Univariate analysis showed only grade to be prognostically significant (p < .03) in determining overall survival. CONCLUSION: Postoperative radiotherapy for unresected or partially resected low-grade astrocytomas produces excellent local control. Higher grade astrocytomas require further investigational studies to improve survival and local control. Grade is prognostically significant with respect to overall survival.

Adolescent↗

PubMed1993

Histopathology of experimental Schistosoma bovis infection in goats.

The inflammatory host response to Schistosoma bovis in young goats was studied at necropsy by light microscopy 34 weeks after primary exposure to 3,000 cercariae (group B, n = 6), 34 weeks after primary exposure to 3,000 cercariae followed by challenge with 2,500 cercariae at week 17 (group C, n = 5), and 17 weeks after primary exposure to 2,500 cercariae, given on week 17 of the experiment (group D, n = 6). Three goats served as uninfected controls. The faecal egg output had been minimal for 17 weeks prior to necropsy in groups B and C and only for the last 2 weeks in group D. Histological studies were carried out on the small intestine, liver, lung and spleen, and tissue egg counts were performed. In sections of the small intestine and liver, a panel of histopathological variables were quantitated to characterize the host response and differences between groups of animals were evaluated with one way analysis of variance. The mean tissue egg count in the small intestine was slightly but not significantly higher in group C than group B and about twice as high in group D (D vs B or C p < 0.01). Group means of numbers of inflammatory foci per section of gut wall corresponded well with those of tissue egg counts, suggesting that the rate of inflammatory destruction of eggs did not differ markedly between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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↗