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Biomedical subjects

A Hallberg

Publications and source records attributed to A Hallberg.

At least 91 records · Page 5Linked to original sources

Hydatidiform mole: a chromosomal search for a recessive mutation.

In a search for minute structural aberrations indicating chromosomal regions of importance for the development of a hydatidiform mole, five diploid androgenetic moles and two partial dispermic moles were examined by high resolution banding technique. The absence of consistent aberrations suggests that either submicroscopical lesion(s) or the ratio of paternal to maternal chromosome complement(s) could be the decisive factor for molar development.

Chromosome Aberrations↗

Dissociation of phosphatidylinositol hydrolysis and insulin secretion of cultured mouse pancreatic islets.

The correlation between hydrolysis of phosphatidylinositol (PI) and insulin secretion was investigated in cultured mouse pancreatic islets. After prelabeling with [3H] glycerol or [3H] inositol, islets were incubated in the presence of different insulin secretagogues. Carbamylcholine induced a rapid decrease of PI-bound radioactivity concurrent with stimulation of insulin secretion, and both these responses were blocked by atropine. After culture at a low (3.3 mM), glucose concentration, carbamylcholine evoked PI hydrolysis, but no insulin secretory response was observed. Carbamylcholine induced PI hydrolysis also under Ca2+-free conditions, which blocked insulin secretion. Stimulation of insulin secretion with high glucose (16.7 mM), K+(25 mM), or arginine (10 mM), or addition of theophylline (5 mM) to high (16.7 mM) glucose, were associated with unchanged rates of PI hydrolysis. In labelling experiments, both carbamylcholine and glucose (16.7 mM) were found to stimulate the incorporation of [3H] inositol into islet PI. These results demonstrate that stimulation of muscarinic cholinergic receptors increases islet PI turnover. There was, however, no general correlation between islet PI turnover and insulin secretion.

Animals↗

Effects of starvation and different culture conditions on the phospholipid content of isolated pancreatic islets.

A colorimetric method for the determination of lipid phosphorus in the nanomolar range was used to determine the total phospholipid content of isolated pancreatic islets. Freshly isolated islets of lean C57BL/6J mice contained significantly more phospholipids expressed per micrograms DNA as compared to C57BL/6J (ob/ob) mouse or Wistar rat islets. Starvation for 48 h (Wistar rats) or 60 h (NMRI mice) did not affect the islet phospholipid content. Phosphatidylcholine was the most abundant phospholipid class of NMRI mouse islets, followed by phosphatidylethanolamine, sphingomyelin, phosphatidylinositol, phosphatidylserine and lysophosphatidylcholine. When islets of NMRI mice were maintained for 5-7 days in tissue culture, the phospholipid content remained unchanged as compared to that of freshly isolated islets despite a considerable loss of the insulin stores. The islet phospholipid content was significantly increased when the glucose concentration of the culture medium was elevated from 3 to 28 mM. Leucine (10 mM) added to a low-glucose medium failed to increase the islet phospholipid content. Addition of glipizide (2 microM) to the culture medium decreased the islet insulin content significantly but failed to affect the total islet phospholipid content. Culture in a Ca2+-free medium containing 28 mM glucose increased the islet insulin content but, again, the phospholipid content remained unaffected. These data show that changes of the total phospholipid content of pancreatic islets are unrelated to the islet insulin content and presumably also to the content of secretory granules. Alterations of the islet content of phospholipids may rather reflect changes of the amount of endoplasmic reticulum of the islet cells.

Animals↗

Effects of chloroquine on lipid metabolism of mouse pancreatic islets.

Pancreatic islets accumulate the amphiphilic drug, chloroquine, which leads to a marked impairment of the insulin production of the B-cells in vitro. In this study the effects of the drug on islet lipid metabolism in vitro were investigated. It was found that exposure of islets to chloroquine (10(-5) M) for one week induced an increase of D-[U-14C]glucose incorporation into phospholipids and triacylglycerols of about two-fold and into diacylglycerols of about six-fold. Furthermore, two-dimensional thin-layer chromatography showed an increased rate of D-[U-14C]glucose incorporation into all major phospholipid classes. A 17% increase of the total islet phospholipid content indicated that an accumulation of islet cell phospholipids occurred. Pulse-chase experiments with D-[U-14C]glucose showed that the rate of degradation of islet phospholipids was decreased after prolonged exposure to chloroquine. No short-term effects of chloroquine upon either the de novo biosynthesis of islet lipids or upon phospholipid degradation could be demonstrated. The present data therefore suggest that chloroquine impairs the rate of islet lipid degradation in long-term experiments, which may be a primary lesion in the sequence of events leading to functional impairment of the B-cell.

Animals↗

Long-term effects of cyclosporin A on cultured mouse pancreatic islets.

In the light of recent attempts to treat newly-diagnosed Type 1 (insulin-dependent) diabetic patients with cyclosporin A, and reports suggesting an impaired glucose tolerance following immunosuppression therapy with cyclosporin A, we investigated the long-term effects of cyclosporin A on islet beta-cell morphology and function in vitro. Collagenase-isolated mouse pancreatic islets were cultured free-floating for 7 days in medium RPMI 1640 + 10% calf serum in the presence of cyclosporin A (0.1 or 1.0 mg/l). Islets cultured in the presence of the higher cyclosporin A concentration had impaired islet proinsulin biosynthesis and insulin release when challenged with high glucose concentration. Moreover, the insulin content of the drug-exposed islets was decreased and so was the rate of DNA synthesis. The glucose oxidation and respiratory rates, however, remained unaffected, suggesting that the impaired insulin production was not a result of defective oxidative metabolism. There were no changes in the ultrastructure or phospholipid biosynthesis of the islets after the drug treatment. These data indicate that cyclosporin A affects islets in culture, the clinical implications of which are so far difficult to assess. The inhibitory effect of cyclosporin A on islet cell DNA synthesis must nevertheless be considered in attempts to ameliorate Type 1 (insulin-dependent) diabetes, and when grating islet cells in numbers primarily insufficient to cure the recipient.

Animals↗

Effects of starvation on phospholipid metabolism of pancreatic islets.

It was the aim of the present study to examine the extent to which starvation-induced impairment of glucose-stimulated insulin secretion is linked to changes of islet phospholipid metabolism. For this purpose both islets isolated from mice starved for 60 hr and islets maintained in culture for 1 week in a low (3.3 mM) glucose medium were studied together with relevant control islets. When challenged with a high glucose concentration the insulin response of both groups of islets was totally blunted. The effect of food restriction on 14C-glucose incorporation into different phospholipid classes was less prominent. On a percentage basis phosphatidylserine biosynthesis of islets isolated from starved mice was most affected, whereas the biosynthesis of phosphatidylcholine was only marginally impaired. Culture of islets for 1 week at the low glucose concentration affected the phospholipid biosynthesis even less and there was only a small decrease of 14C-glucose incorporation into phosphatidylcholine. In general, cultured islets synthesized more phospholipids than the freshly isolated ones. No dose-response relationship was found between various degrees of glucose-stimulated insulin secretion and 14C-glucose incorporation into different phospholipid classes of islets isolated from fed mice. The present data thus provided no evidence that an impairment of the islet phospholipid turnover contributes to the starvation-induced impairment of insulin secretion. There was also no close correlation between phospholipid biosynthesis in terms of 14C-glucose incorporation and glucose-stimulated insulin secretion.

Animals↗

Myasthenia gravis. Immunological studies in a young child treated with thymectomy and immunosuppressive drugs.

A case of severe myasthenia gravis diagnosed in a 12-month-old girl is described. Thymectomy at 15 months of age had only a negligible effect on the course of the disease. Treatment with cholinesterase inhibitors, prednisolone and azathioprine was started. After one year of combined treatment she was symptomfree and 3 years later treatment with cholinesterase inhibitors and prednisolone was discontinued. Attempts to withdraw azathioprine have so far been unsuccessful, leading to relapse of the disease. IgG-antibodies against cholinergic receptors were lowered to near normal, whereas the levels of total plasma immunoglobulins remained normal. The proportion of T-lymphocytes in peripheral blood was reduced during the first weeks after thymectomy, but has since been normal. Lymphocyte function measured by PHA stimulation remained normal all the time. The girl grew and developed normally without complicating infectious diseases in spite of her severe disease, thymectomy and immunosuppressive treatment.

Autoantibodies↗

Lymphocyte receptors for human erythrocytes in newborn infants and adults. Expression on fresh and lectin-stimulated cells.

Lymphocyte receptors for human erythrocytes (HRBC) have been demonstrated by an optimized technique using neuraminidase-treated HRBC and high-protein diluent. Mean values of 55 and 50% reactive lymphocytes were found in the peripheral blood of newborn infants and adult donors, respectively. The HRBC receptor was labile under tissue culture conditions in vitro, in contrast to the receptors for sheep erythrocytes, Fc of IgG, and complement. Short-term culturing of lymphocytes with T cell mitogens (phytohemagglutinin, concanavalin A) increased the proportion of HRBC-receptor-bearing lymphocytes. Pokeweed mitogen, being mainly a B cell stimulator, was less effective in activating lymphocytes to resynthesize the receptor. It is concluded that the HRBC receptor is probably not a stable marker for a single subpopulation of human T lymphocytes. During the first week of life, the HRBC receptor is expressed on at least the same proportion of peripheral blood lymphocytes as in adults.

Adult↗

Effect of a hypoglycaemic sulphonylurea (HB419) and a non-metabolizable amino acid (BCH) on the insulin release and endogenous substrate metabolism of rat pancreatic islets.

The effects of the hypoglycaemia sulphonylurea glibenclamide (HB419) and the non-metabolizable leucine analogue beta-2-aminobicyclo(2.2.1)heptane-2-carboxylic acid (BCH) on insulin release and endogenous substrate metabolism were studied in isolated rat islets. Pre-labelling of the endogenous islet substrate was performed with [14C]glucose (20 mM) or [14C]glutamine (10 mM) during a 24 h tissue culture period before measurements of insulin release or 14CO2 production in short-term incubations. Both HB419 and BCH stimulated the insulin release of the cultured islets, although BCH only after culture of islets with glutamine. The rate of labelling of the islets with [14C]glucose reached an apparent plateau after 16 h in culture and the total islet accumulation of glucose carbon over the 24 h period averaged 12.9 +/- 3.0 nmol/25 islets. Less than 0.5% of the glucose residues was converted to glycogen whereas lipids represented about 2.5%. Fractionation of lipids showed 67% phospholipids, 18% triacylglycerols, 11% diacylglycerols and 6% non-esterified fatty acid. The islet accumulation of glutamine during 24 h corresponded to 11.5 +/- 1.5 nmol/25 islets. After pre-labelling of islets with [14C]glucose there was no effect on the 14CO2-evolution over a 30 min incubation period of either HB419 or BCH. There was also no effect of HB419 after pre-labelling with [14C]glutamine, whereas, in this latter situation, a significant stimulation was observed with BCH. It is concluded that the effects on the pancreatic B-cells by antidiabetic sulphonylureas are not mediated via nutrient receptors.

Amino Acids↗

Natural killer cell activity and antibody-dependent cellular cytotoxicity in newborn infants.

The ability of lymphocytes from the peripheral blood of preterm and term infants and adult women and men to mediate natural killing (NK) and K cell activity (antibody-dependent cellular cytotoxicity) was analysed in 4 hours 51Cr-release assays. K 562 cells were targets for NK activity. K cell activity was assayed on antibody-coated rat thymocytes. Lymphocytes from adult male donors were significantly more cytotoxic to K 562 cells than were lymphocytes from adult female donors. Lymphocytes from both preterm and term infants had significantly lower NK and K cell activity than lymphocytes from adult donors. During the first month of life no increase in NK activity or K cell activity occurred in 7 infants who were re-examined. It is concluded that neither NK nor K cell activities are fully developed during the first month of life.

Adult↗

PPD testing as a diagnostic aid in non-tuberculous mycobacteriosis. Clinical and immunological investigations in 4 children with cervical lymphadenitis.

Four children suffering from unilateral cervical lymphadenitis with histopathological changes typical of mycobacteriosis were seen during a short time. None of the Children had been BCG vaccinated. Mycobacteria belonging to the Myobacterium aviumintracellulare complex were isolated from excised lymph nodes in two of the patients. Intracutaneous tests with PPD from M. tuberculosis were negative in all the children, whereas two children responded to each of 3 PPDs prepared from atypical mycobacteria. Two patients were unreactive in all the skin tests. Lymphocyte transformation tests in vitro with a battery of various PPDs indicated sensitization to atypical mycobacteria in two children, one of which was negative in the skin tests. All the patient had normal plasma Ig concentrations but two patients had low proportions of T lymphocytes in the peripheral blood. One of these also had reduced total numbers of T cells. Nevertheless, lymphocyte responses in vitro to phytohaemagglutinin were normal in all the children. The results show that cutaneous and in vitro tests with a battery of different PPDs have a place as diagnostic adjuncts in atypical mycobacteriosis. We suggest that immunological competence is analysed in such patients.

Child, Preschool↗

Pneumonia associated with Chlamydia trachomatis infection in an infant.

Chlamydia trachomatis was isolated from the epipharynx of a 10-week-old baby girl taken ill with pneumonia but without signs of conjunctivitis. The infant developed specific antibodies to the organism. The course of the pneumonia was protracted, with cough and tachypnea. The baby, who was afebrile, improved on antibiotic therapy but pulmonary infiltrates persisted for several months. To our knowledge, this is the first case of pneumonia in an infant associated with C. trachomatis infection reported elsewhere than North America.

Chlamydia Infections↗

Release of insulin in vitro from normal and duct-ligated rat pancreas.

Ligation of the pancreatic duct causes atrophy of the acinar cells but leaves the endocrine tissue intact. In the present study, a partial ligation of the pancreatic duct was performed in the rat, and the in vitro insulin response to glucose was compared from both the atrophic and non-atrophic portions of the pancreas. Subsequent morphological studies of the duct-tied portion of the pancreas indicated a complete lack of acinar cells and a possible neoformation of ducts, fat cells and connective tissue. However, islets were present in normal amounts and appeared well perserved. Measurements of the insulin release in vitro from this ligated pancreatic tissue showed that an increase of the glucose concentrations from 3.3 to 16.7 mmol/1 resulted in a six-fold stimulation. A further two-fold stimulation was seen after addition of theophylline to the high-glucose incubation medium. In addition, only under the latter conditions was there a significantly increased insulin release from both non-atrophic portion of the pancreas and from the pancreas of sham-operated animals. It is concluded that duct ligation does not diminish the glucose sensitivty of rat islet B-cells. Thus, the present study does not support the view proposed previously that islet tissue is functionally of a foetal nature following duct ligation.

Animals↗

Receptors for immunoglobulin and complement on sheep RBC-binding lymphocytes in newborn infants.

Sheep erythrocyte-binding human peripheral blood lymphocytes bearing receptors for the Fc-part of IgG and/or complement were studied in twenty newborn pre-term and term infants and fifteen adult controls. A technique with mixed rosettes and fluorescein-labelled sheep erythrocytes was used. The newborn infants had a significantly lower proportion of lymphocytes with receptors for sheep erythrocytes and the Fc-part of IgG (1.6%) than the adults (6.7%). Also the percentage of lymphocytes binding both sheep erythrocytes and complement-coated indicator cells was significantly lower in the newborn infants (2.6%) than in the adults (8.9%). A significantly higher proportion of lymphocytes had receptors for sheep erythrocytes and complement than for sheep erythrocytes and the Fc-part of IgG in both newborn infants and adults. There was no correlation between the values of lymphocytes binding sheep erythrocytes, or the Fc of IgG or complement and the proportion of mixed rosettes.

Adult↗

Evolution of three lymphocyte markers in newborn, preterm infants.

Nine newborn, preterm infants have been studied at the ages of 1-3 days, 8-10 days and 22-24 days for surface markers on peripheral blood lymphocytes. As compared to adult controls, four of the infants had a low proportion of sheep RBC binding lymphocytes at birth, but at 1-3 weeks of age all infants had reached the adult level. Lymphocyte receptors for Fc of IgG and for complement, although both mainly characterizing non-T cells, evolved differently post partum: the proportion of Fc-receptor-bearing lymphocytes tended to increase with age of the infant, whereas already at birth complement receptor-bearing lymphocytes were at or above the adult level.

Animals↗

Maternal and paternal origin of extra chromosome in trisomy 21.

Fluorescence markers were studied in 40 patients with Down's syndrome and their parents. In 11 cases maternal and in 5 cases paternal non-disjunction could be shown. The disjunctional event occurred in the first meiotic division in 5 maternal and in 2 paternal cases. A second division failure was found in 4 maternal and 2 paternal cases. In 3 cases the failure could either be of first or second meiotic division origin.

Adult↗