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Biomedical subjects

K Andersson

Publications and source records attributed to K Andersson.

375 records · Page 21Linked to original sources

Neurocircuitry of the basal ganglia studied by monitoring neurotransmitter release. Effects of intracerebral and perinatal asphyctic lesions.

The neurocircuitries of the basal ganglia are studied with in vivo microdialysis, with special consideration to dopamine transmission and its interaction with other neurotransmitter systems. The aim is to develop experimental models to study the pathophysiology and therapy of neurodegenerative disorders of the basal ganglia, as well as to develop models to study the short- and long-term consequences of perinatal asphyctic lesions. A main goal of these studies is to find and to characterize new treatments for these disorders.

Alzheimer Disease↗

Inflammatory response in the rabbit after phacoemulsification and intraocular lens implantation using a 5.2 or 11.0 mm incision.

PURPOSE: To study the effect of two incision sizes, 5.2 and 11.0 mm, on the inflammatory response in rabbit eyes after lens extraction with phacoemulsification. SETTING: S:t Erik's Eye Hospital, Stockholm, and Pharmacia, Uppsala, Sweden. METHODS: Bilateral endocapsular phacoemulsification was performed on 32 rabbits. The wound was enlarged to 5.2 mm, and a poly(methyl methacrylate) intraocular lens (IOL) was implanted in the capsular bag. In each rabbit, one eye was selected at random and the wound in that eye enlarged to 11.0 mm. In both eyes the wound was sutured with a 9-0 polypropylene continuous suture. The number of white blood cells (WBCs) and prostaglandin E2 (PGE2) in the aqueous humor were measured at days 1, 3, 7, and 28 postoperatively. Corneal thickness was also measured by pachymetry. RESULTS: The number of WBCs at day 3 and the PGE2 levels at days 1, 3, and 7 were significantly higher in eyes with 11.0 mm incisions than in eyes with 5.2 mm incisions. One week after surgery, the corneas in the eyes with 11.0 mm incisions were significantly thicker than in those with 5.2 mm incisions. CONCLUSION: The results indicate that incision size is an important factor in the inflammatory response following phacoemulsification and IOL implantation in the rabbit eye.

Animals↗

Three-dimensional structure of a specific pre-messenger RNP particle established by electron microscope tomography.

Electron microscope tomography has been used to refine the structural analysis of individual RNP particles synthesized on Balbiani ring genes in Chironomus tentans. The spherical particles have a diameter of 500 A and are composed of a thick RNP ribbon bent into an asymmetrical, four-domain, ring-like configuration. The first domain, containing the 5' end of the transcript, and the fourth domain, containing the 3' end, are close to each other.

Animals↗

Recurrent genital herpes in a population attending a clinic for sexually transmitted diseases.

Patients with recurrent genital herpes attending a sexually transmitted disease clinic were studied and transmission of the infection was elucidated by evaluating serostatus in their partners. Of 84 patients attending for recurrent genital herpes, 94% had a herpes simplex virus type 2 (HSV-2) infection and only 6% (5 patients) a type 1 infection. The mean age of the patients was 36 years and the duration of their infection was up to 37 years (median 4 years). In most patients the number of recurrences had not decreased between the first year and the last year. About half had experienced a more severe first episode infection. Of the patients, 64% were not aware of asymptomatic shedding and the risk of sexual transmission without clinical symptoms. Of 67 steady partners of patients with genital HSV-2, 15% had a history of genital herpes. By HSV serology, HSV-2 antibodies (indicating subclinical genital herpes) were demonstrated in more than half of the partners. The duration of the relationship or condom use did not seem to influence the frequency of transmission to the partner, which may indicate an individual susceptibility for acquiring a genital HSV-2 infection. Eleven per cent of the patients were on suppressive antiviral therapy, while 39% had no experience of antiviral therapy. Type-specific HSV serology was found to be of value in counselling partners of patients with genital herpes.

Adolescent↗

The effects of short-term parenteral nutrition on human liver protein and amino acid metabolism during laparoscopic surgery.

BACKGROUND: This study was undertaken to elucidate the specific effects of short-term artificial nutrition on human liver protein metabolism. METHODS: Thirty patients undergoing elective laparoscopic cholecystectomy were studied: a control group (n = 16) and a group that received total parenteral nutrition (TPN; n = 14). The nutrition consisted of a balanced i.v. solution of nutrients (17.5 nonprotein kcal/kg body wt, 50% fat, 50% carbohydrates, and 0.1 gN/kg) that was discontinued when the investigation was finished, after a total infusion time of 8.6 +/- 1.0 hours. A liver biopsy specimen was taken as soon as possible after surgery was started, for the determination of the free hepatic amino acid concentrations. In 16 of the patients, L[2H5]phenylalanine was given by i.v. to determine the fractional synthesis rate of total liver protein in a second liver biopsy specimen taken approximately 30 minutes later. RESULTS: The fractional synthesis rate of total liver protein was 15.2% +/- 4.7%/d in the TPN group (n = 7), which was not different from that of the control group (17.7% +/- 3.8%/d, n = 9). However, the free hepatic concentrations of alanine (p < .05) and the essential amino acids increased (p < .001) in the TPN group, whereas the total hepatic amino acid concentrations were comparable between the groups. CONCLUSION: Thus short-term TPN induced specific changes of the free hepatic amino acid concentrations, whereas total liver protein synthesis remained unaffected by the nutrition.

Adult↗

Nasal hyperreactivity among teachers in a school with a long history of moisture problems.

Upper airway symptoms have frequently been reported in people working or residing in damp buildings. However, little information has been available on objective pathophysiologic findings in relation to these environments. Twenty-eight teachers, who had worked for at least five years in a recently renovated school that had had severe moisture problems for years, were randomly selected for this study. Eighteen teachers, who had worked in another school that had no moisture problems, were randomly selected to serve as the control group. Although remedial measures had been taken, an increase in the prevalence of mucous membrane irritations was still reported by the teachers in the target school. We used a nasal challenge test with three concentrations of histamine (1, 2 and 4 mg/mL). Recordings of swelling of the nasal mucosa were made with rhinostereometry, a very accurate optical non-invasive method. The growth curves of mucosal swelling induced by the three concentrations of histamine differed significantly between the two groups (p < 0.01). The frequencies of atopy, evaluated with the skin-prick test, were almost identical in both groups. The study indicates that long-term exposure to indoor environments with moisture problems may contribute to mucosal hyperreactivity, of the upper airways. Such hyperreactivity also seems to persist for at least one year after remedial measures have been taken.

Air Pollution, Indoor↗

Nasal histamine provocation of tenants in a sick-building residential area.

Health problems associated with the indoor climate have aroused an increasing scientific interest, and the term "sick-building syndrome" (SBS), which describes the most frequent symptoms in this context, has been coined. However, it has been difficult to demonstrate objectively any pathophysiological changes in the subjects affected. Thirty-three healthy and nonatopic persons were randomly selected on the basis of answers in a postal questionnaire dealing with discomfort or health symptoms experienced in their home environment. Twenty-three lived in a residential area with indoor climate problems (SBS area) and 10 lived in an area without climate problems (non-SBS area). Twelve persons from the SBS area reported nasal symptoms, which they ascribed to their home environment. The remaining 11 persons from the same area, as well as the 10 subjects from the non-SBS area, had no nasal distress. They were examined with rhinostereometry during histamine provocation. Hyperreactivity, defined as mucosal swelling exceeding 0.4 mm at 5 and 10 minutes after provocation with 0.14 ml of 2 mg/ml histamine chloride, was frequent in the symptomatic SBS group as well as in the asymptomatic SBS group. The analysis of the increment of mucosal swelling for the whole range of histamine chloride concentrations (0.1 mg/ml to 16 mg/ml) showed significantly different growth curves for the three groups in the residential areas and an external reference group, (p < 0.0001). Subjects living in the SBS area were prone to nasal hyperreactivity, whether they reported symptoms from the upper airways or not. The results support the hypothesis that living in an SBS area increases the risk of developing nonspecific nasal hyperreactivity.

Adult↗

Physiological significance of ECL-cell histamine.

In the oxyntic mucosa of the mammalian stomach, histamine is stored in ECL cells and in mucosal mast cells. In the rat, at least 80 percent of oxyntic mucosal histamine resides in the ECL cells. Histamine is a key factor in the regulation of gastric acid secretion. Following depletion of ECL-cell histamine by treatment with alpha-fluoromethylhistidine (alpha-FMH), basal acid secretion was reduced, and gastrin-stimulated acid secretion was abolished. Vagally-induced acid secretion (by insulin injection or pylorus ligation) was unaffected by alpha-FMH treatment but inhibited by an H2 antagonist. These results suggest that gastrin stimulates acid secretion via release of ECL-cell histamine, whereas vagally-induced acid secretion--although histamine-dependent--does not rely on ECL-cell histamine. Gastrin is known to have a trophic effect on the oxyntic mucosa. By combining long-term hypergastrinemia with continuous infusion of alpha-FMH, we were able to show that gastrin-evoked trophic effects in the stomach do not depend on ECL-cell histamine.

Animals↗

ECL cell morphology.

Using immunohistochemistry at the conventional light, confocal and electron microscopic levels, we have demonstrated that rat stomach ECL cells store histamine and pancreastatin in granules and secretory vesicles, while histidine decarboxylase occurs in the cytosol. Furthermore the ECL cells display immunoreactivity for vesicular monoamine transporter type 2 (VMAT-2), synaptophysin, synaptotagmin III, vesicle-associated membrane protein-2, cysteine string protein, synaptosomal-associated protein of 25 kDa, syntaxin and Munc-18. Using electron microscopy in combination with stereological methods, we have evidence to suggest the existence of both an exocytotic and a crinophagic pathway in the ECL cells. The process of exocytosis in the ECL cells seems to involve a class of proteins that promote or participate in the fusion between the granule/vesicle membrane and the plasma membrane. The granules take up histamine by VMAT-2 from the cytosol during transport from the Golgi zone to the more peripheral parts of the cells. As a result, they turn into secretory vesicles. As a consequence of stimulation (e.g., by gastrin), the secretory vesicles fuse with the cell membrane to release their contents by exocytosis. The crinophagic pathway was studied in hypergastrinemic rats. In the ECL cells of such animals, the secretory vesicles were found to fuse not only with the cell membrane but also with each other to form vacuoles. Subsequent lysosomal degradation of the vacuoles and their contents resulted in the development of lipofuscin bodies.

Animals↗

The biology and pathobiology of the ECL cells.

The enterochromaffin-like (ECL) cells represent the predominant endocrine cell population in the acid-producing part of the stomach of both experimental animals and man. These cells actively produce and store histamine in addition to an anticipated but as yet unidentified peptide hormone and are under the control of gastrin. An acute gastrin stimulus causes exocytosis of the cytoplasmic granules/vesicles (and release of histamine and activation of the histamine-forming enzyme, histidine decarboxylase), while a more sustained gastrin stimulus causes first hypertrophy and then hyperplasia of the ECL cells in the rat (at most, a fivefold increase in the cell number). These effects can be demonstrated following infusion of gastrin or following an increase in the concentration of circulating gastrin of endogenous origin. The growth of the ECL cells reflects an accelerated self-replication rate. As studied in the rat, the self-replication rate is accelerated quite soon after induction of hypergastrinemia (blockade of acid secretion), the rate is maximally elevated within two weeks and then declines to control values at ten and 20 weeks despite the sustained hypergastrinemia. Lifelong hypergastrinemia in rats is associated not only with ECL-cell hyperplasia but also with an increased incidence of ECL-cell carcinoids. Recently, we could show that alpha-fluoromethylhistidine, which is a suicide inhibitor of histidine decarboxylase, effectively depletes the ECL cells of histamine and that the histamine-depleted ECL cells respond to gastrin with hyperplasia in a manner identical to normal ECL cells. Other factors beside gastrin seem to participate in the control of ECL-cell function and proliferation. Although exogenous somatostatin is known to suppress the activity of the ECL cells, we have failed to obtain evidence that the somatostatin cells in the oxyntic mucosa play a role in the physiological control of the ECL cells. The vagus, however, is important for the ability of the ECL cells to respond to gastrin. This conclusion is based on the observation that vagal denervation suppresses the hyperplastic response of the ECL cells to gastrin. Porta-cava shunting, on the other hand, greatly enhances the responsiveness of the ECL cells to gastrin. The mechanism behind this effect is unknown.

Animals↗

A charcoal sampling method and a colorimetric analytical procedure for carbon disulfide. Measurement data from a viscose rayon manufacturing plant.

A charcoal sampling method and a colorimetric analytical method for carbon disulfide were developed. The methods were validated at relevant concentration of CS2. Precision and accuracy were acceptable (23%-6% and 36%-1%) at 25-400 micrograms CS2 deposited on the solid sorbent. The methods were calibrated with charcoal tube sampling and GC-FPD analysis. Regression analysis was performed on duplicate samples and a correlation coefficient of 0.96 and a regression coefficient of 0.8 were obtained. Occupational hygiene measurements were performed in a rayon manufacturing plant. A great proportion of TWA concentrations exceeded the swedish TLV (16 mg/m3) at all sample sites.

Air Pollutants, Occupational↗

The biology and physiology of the ECL cell.

The enterochromaffin-like (ECL) cells, which are the predominant endocrine cell type in the acid-producing part of the vertebrate stomach, are characterized by numerous, electron-lucent vesicles and few electron-dense granules in the cytoplasm. The biological and physiological significance of the ECL cells remains poorly understood. They produce and store histamine and pancreastatin and are thought to produce an as yet unidentified peptide hormone. The most important clue to their function is their willingness to respond to changes in circulating gastrin. The present review presents current knowledge of the biology and physiology of the rat stomach ECL cells. Examination of serially sectioned ECL cells has revealed that the cytoplasmic vesicles almost invariably contain an electron-dense core, suggesting that perhaps the distinction between granules and vesicles is artificial. We propose a life cycle of the secretory organelles in the ECL cells with a progressive development from granules to vesicles. The results showed that the gastrin-evoked release of histamine and pancreastatin was accompanied by loss of vesicles, and that synthesis of histamine and pancreastatin was accelerated by sustained infusion of gastrin, a treatment that was associated with renewal of vesicles. The events described are instrumental in bringing about a change in the "steady state" or "equilibrium" of the ECL cells, from a non-stimulated, resting state to a gastrin-stimulated, active state. This change is attained within six to eight hr. The next "steady state" change is that from "normal-sized" but active ECL cells to "hypertrophic" ECL cells. The increase in cell size is complete after about one week. The gastrin-evoked increase in the ECL cell self-replication rate is maximal after about 10 days, after which time there is a gradual return back to pre-stimulation values. The ECL cell density increases fairly slowly and does not reach maximum (four-fold increase) until after 20 weeks hypergastrinemia. The activity of the histamine-forming enzyme, histidine decarboxylase, is elevated by gastrin and remains elevated for as long as the gastrin stimulus is maintained (the longest time studied was 20 weeks). The physiological significance of the ECL cells is probably related to their capacity to produce and store histamine and an as yet unidentified peptide hormone. The ECL cells are thought to be the source of histamine necessary for the gastrin-evoked acid response. In addition, preliminary evidence suggests that the ECL cells and the anticipated ECL cell hormone play a role in bone formation.

Animals↗

Intrauterine or oral administration of levonorgestrel in combination with estradiol to perimenopausal women--effects on lipid metabolism during 12 months of treatment.

OBJECTIVE: Limited data concerning serum lipids and lipoproteins are available on the effect of HRT in perimenopausal women, who commonly have marked bleeding disturbances and may have severe climacteric symptoms. Almost all previously published data have utilized a simplified form of lipoprotein analysis, which includes an estimation and not a determination of LDL cholesterol. To delineate the role of locally administered progestogen, perimenopausal women were studied for a year. PATIENTS AND METHODS: 40 perimenopausal women with climacteric complaints. The continuous release of low-dose levonorgestrel from an intrauterine device was used as progestogen co-medication to estradiol in a new type of continuous combined hormone replacement therapy. Women were randomized to either cyclical treatment with 2 mg of oral estradiol valerate in combination with 250 micrograms of levonorgestrel for the last ten days (Cyclo Progynova) or continuously with 2 mg estradiol valerate orally in combination with a 20 micrograms per 24 hour levonorgestrel releasing intrauterine device. RESULTS: Reduced HDL cholesterol was initially recorded in both treatment arms and disappeared after 1 year of treatment. Triglycerides were reduced in the orally treated group, but not in the device group. No changes in LDL cholesterol were noted. CONCLUSIONS: The findings suggest that continuous combined HRT with intrauterine release of 20 micrograms levonorgestrel per 24 hours in perimenopausal women is neutral as far as lipid metabolism is concerned, since no alterations compared with pretreatment values could be noted after 12 months of treatment. Less marked lipid changes were obtained in perimenopausal women as compared with data on postmenopausal women. Differences in methodology may partly account for this.

Administration, Oral↗