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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 811 records · Page 45Linked to original sources

[Results of follow-up examinations after reduction mammoplasty].

164 patients in whom reduction mammoplasty according to Strömbeck had been performed, were followed up and questioned by means of a questionnaire as regards improvement of their preoperative complaints and their satisfaction with the success of the operation. 93% of the complaints were removed or at least alleviated. New complaints occurred in 16% of the women due to the visibility of the scars and scar pain. 51% of the women stated that the operation had been fully satisfactory, whereas 46% made some reservation and 3% were dissatisfied. The following complications were observed: 4 partial necroses of the mammillae, 2 haematomas, 2 wound infections, 2 fatty tissue necroses and 26 secondary sutures. The complications at the mammillae and the blood losses were found to correlate with the amount of resected weight. However, surgical experience was also an important factor, both as regards the complication rate and the cosmetic result, especially in cicatrisation and the shape and seat of the mammillae. On the whole, 69% of the results can be classified as "good", 30% as "satisfactory" and 1% as "poor".

Adolescent↗

[Significance of elevated hemoglobulin A1c for the pathogenesis of diabetic retinopathy].

The hemoglobin of 70 diabetics with retinopathy was analysed. 56 patients had pathologically elevated values, 12 values were within the upper normal limit and in 2 cases the findings were normal. This hemoglobin variant is characterized by an increased affinity of oxygen. Clinically and pathologically speaking the elevated HbA1c value could be a causal factor in diabetic retinopathy. Comparisons with sickle cell anemia and thalassemia seem to indicate that hemoglobinopathy and retinopathy are pathogenetically related.

Diabetic Retinopathy↗

Amino acids and lipoproteins in plasma of duodenopancreatectomized patients: effects of glucagon in physiological amounts.

Duodenopancreatectomy induces a severe glucagon deficiency and elevated plasma concentrations of alanine, aspartate, glycine, proline, serine, arginine, citrulline, ornithine, phenylalanine and tyrosine. Restoring high physiological plasma glucagon in six such patients by infusing 0.3 mg/24 h of exogenous glucagon reduced significantly (P less than 0.01 or 0.001) the mentioned amino acids (except phenylalanine) and further asparagine, glutamine, methionine and threonine. In six normal subjects the same infusion reduced significantly (P less than 0.05 to 0.001) plasma alanine, asparagine, glutamate, glutamine, glycine, proline, serine, threonine, arginine, ornithine, lysine and tyrosine. However, the effect was significantly (P less than 0.01 or 0.001) less marked for alanine, glutamine, glycine, methionine, serine, threonine and arginine. This particular glucagon sensitivity of duodenopancreatectomized patients suggests that glucagon deficiency is the cause of their hyperaminacidaemia. By contrast, lipoprotein concentrations were virtually unaffected by either glucagon deficiency or its replacement. In the light of the marked hypoaminacidaemia in glucagonoma patients these results attribute to glucagon a major role as a regulator of protein metabolism.

Amino Acids↗

Ontogeny of the secretory pattern of LH and FSH in male mice during sexual maturation.

Plasma LH and FSH concentrations were measured in male mice at 10-day intervals from 1 to 90 days and at 2-day intervals between 20 and 40 days. The skewed distribution and variability of LH concentrations observed in mice aged 20 to 90 days suggests that LH is released in an episodic fashion. Mean levels of LH and baseline concentrations increased significantly from infantile (1-20 days) to adult age (50-90 days). Pulsatile discharges of LH appeared to start at 22 days, and their frequency increased from 9.6% (prepubertal stage: 20-30 days) to 31.6% (pubertal stage: 30-40 days). In contrast, for FSH no evidence of pulsatile secretion was found, and mean levels increased 5-fold from the infantile to the peripubertal stage, and adult levels were then attained.

Age Factors↗

Localization of complement component 3 on Streptococcus pneumoniae: anti-capsular antibody causes complement deposition on the pneumococcal capsule.

We have previously shown that complement component 3 (C3) deposited onto encapsulated Streptococcus pneumoniae by anti-capsular antibody (Ab) is a more efficient opsonin in vitro and in vivo than C3 deposited by anti-cell wall Ab (Brown et al., J. Clin. Invest. 69:85-98, 1982). In the present study, we explored the cellular location of C3b molecules that differ in opsonic efficiency by using avidin-ferritin to localize biotinylated Ab and C3 molecules on S. pneumoniae for electron microscopy. Anti-cell wall Ab and C3b molecules deposited by this Ab on unencapsulated S. pneumoniae were localized to S. pneumoniae cell walls. Anti-capsular Ab and C3b deposited by this Ab were seen in clusters on encapsulated S. pneumoniae at a distance from the cell wall. However, no avidin-ferritin staining of encapsulated S. pneumoniae was seen on incubation with biotinyl-anti-cell wall Ab, biotinylated C3 fixed by anti-cell wall Ab, or nonimmune serum containing biotinyl-C3. In each case, uptake of the biotinylated component was proven by radioactivity measurements, since biotinylated Ab and C3 were also radiolabeled with 125I. When avidin-ferritin did not bind to biotinylated components. Ouchterlony analysis indicated that C3 was bound to cell wall components on the encapsulated organisms. Thus, we conclude that, for encapsulated S. pneumoniae, opsonically efficient C3b molecules, deposited by anti-capsular Ab, are located on the S. pneumoniae capsule, whereas the opsonically inefficient C3b molecules deposited by anti-cell wall Ab or nonimmune serum are located on the cell wall. A major reason for the increased virulence of encapsulated compared to unencapsulated S. pneumoniae is that, in the absence of anti-capsular Ab, the S. pneumoniae capsule interferes with the recognition of cell wall-bound C3b molecules by phagocytic cell receptors.

Antibodies, Bacterial↗

Classical complement pathway activation by antipneumococcal antibodies leads to covalent binding of C3b to antibody molecules.

We have examined whether or not a physical relationship exists between antipneumococcal antibodies (Ab) and C3b when Ab activate the classical complement pathway on the surface of pneumococci (Pn). After sensitization with 125I-labeled Ab, Pn were sequentially incubated with purified C1, C4, C2, and biotinylated C3. Ab molecules were then eluted from Pn, and C3b-associated molecules were purified on avidin-Sepharose. Both 125I-labeled immunoglobulin G (IgG) and [125I]IgM bound to C3b; the association was stable to incubation in 1% sodium dodecyl sulfate at 37 degrees C. The association was only partially reversed by incubation in 1 M hydroxylamine-0.5% sodium dodecyl sulfate (pH 10.5), implying that Ab and C3b were linked by amide as well as ester bonds. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of dithiothreitol and NH2OH eluates from the avidin-Sepharose showed that C3b bound to both heavy and light chains of the Ab. Moreover, the ability to bind to erythrocyte C3b receptors could be transferred to unsensitized Pn by eluates from Pn on which Ab had activated the classical pathway. These covalent complexes of Ab and C3b may be especially important in the opsonization of Pn by Ab and complement.

Animals↗

Testicular response to HCG stimulation and sexual maturation in mice.

2 IU HCG/10 g body weight were administered intraperitoneally to male mice at 1, 20, 30, 40, 60 and 90 days of age. Testosterone was quantified by radioimmunoassay 1 h later in the plasma and the testes. At all stages studied HCG significantly increased testicular and circulating testosterone over the concentrations determined in saline-injected controls. The testicular response to HCG stimulation was age-dependent, it increased from birth to sexual maturity, particularly between 20 and 40 days. This study demonstrates that the testicular responsiveness is probably an important factor in the sexual maturation of mice, especially for the pubertal increase of androgens.

Animals↗

Cyclooxygenase products and cyclic nucleotide levels with infusion of arachidonic acid, PGI2, PGE2, PGF2, and 6-keto-PGF1 in an isolated dog lung.

Arachidonic acid (AA) was infused into the pulmonary artery of an isolated dog lung perfused with a physiologic salt solution. This led to elevations in pulmonary cyclic AMP and prostaglandins (PGs) including PGE2, PGF2 alpha, TXB2 (a metabolite of TXA2), and 6-keto-PGF1 alpha (a metabolite of PGI2). The elevations were prevented by PG synthesis inhibitors. A dose of PGI2 comparable to that produced from AA led to elevations in cyclic AMP. These elevations were not reduced by PG synthesis inhibitors; this indicated that the inhibitors did not reduce cyclic AMP except by inhibiting metabolism of AA. The PGE2 led to lesser elevations in cyclic AMP than did PGI2; PGF2 alpha and 6-keto-PGF1 alpha did not increase cyclic AMP. Levels of cyclic AMP were not elevated. We conclude that some of the elevation in cyclic AMP from AA was most likely from production of PGs since elevations in both were prevented by the inhibitors. However, the possibility remains that AA metabolites other than PGs also contributed to elevations in cyclic AMP. We also conclude that PGI2 most likely accounted for some of the cyclic AMP elevation from AA since PGI2 could be readily produced in amounts that elevate cyclic AMP. However, the possibility remains that PGE2, the less consistent cyclic AMP stimulators (l.e., PGF2 alpha and 6-keto-PGF1 alpha), TXA2 or TXB2, or PGs not measured in this study also contributed to the elevations in cyclic AMP from AA.

6-Ketoprostaglandin F1 alpha↗

Partial characterization and clinical correlation of circulating human immunoglobulins directed against thyrotrophin binding sites in guinea pig fat cell membranes. Development of a direct enzyme immunoassay.

To obviate several problems inherent in indirect thyroid-stimulating hormone (TSH) receptor antibody assays, we developed an enzyme-linked immunosorbent assay (ELISA) that measures antibodies binding to guinea pig fat cell membrane, which contain high concentrations of TSH receptors. Solubilized guinea pig fat cell membranes were adsorbed to plastic microtiter plates and served as the solid-phase antigen. Test sera and affinity-purified alkaline phosphatase-conjugated anti-human IgG were co-incubated with membranes, after which p-nitrophenyl phosphate was added. Results were read when a positive control reached a standard color change (OD405nm). Specificity of this assay was demonstrated by the inability of albumin, insulin, TSH subunits, propranolol, or dexamethasone to block binding 30. normal subjects had a mean OD value of 0.080 +/- 0.050 (SD). 23 of 25 untreated Graves' patients had OD values at least 2 SD above the normal mean (Grave's mean +/- SD; 0.46 +/- 0.33, P less than 0.001) and in each case 10(-6) M TSH inhibited the binding by at least 60%, suggesting that the immunoglobulins were directed at the TSH receptor. Seven of 25 serum samples from patients with Hashimoto's disease, seven of 23 serum samples from patients with transient hyperthyroidism (subacute thyroiditis or painless thyrotoxic thyroiditis), and two of 10 samples from patients with thyroid carcinoma had significant elevations in the titers of membrane-directed immunoglobulins. Graves' patients who were treated with ablative therapy at least 6 mo earlier and who were euthyroid when restudied continued to have abnormally elevated membrane-directed immunoglobulins in six of eight samples studied. Further studies involved the substitution of affinity-purified alkaline phosphatase anti-IgM antisera for the anti-IgG antisera routinely used. Seven of 12 serum samples from patients with Graves' disease had significant elevations in binding which in every instance was inhibited by greater than 60% by 10(-6) M TSH. In sum, the present results indicate that (a) we have developed a sensitive, specific, reproducible, convenient ELISA for the measurement both of the total amount of circulating membrane-directed antibodies and of TSH-displaceable membrane-directed immunoglobulins. (b) This ELISA detected significant elevations in TSH-displaceable guinea pig membrane binding in 23 of 25 untreated Graves' patients as well as in approximately 30% of patients with Hashimoto's thyroiditis and subacute thyroiditis. (c) Elevated membrane directed antibodies may continue to be present many months or years after restoration of the euthyroid state. (d) Circulating membrane binding IgM immunoglobulins have been detected in patients with Graves' disease. Further studies using this ELISA should prove useful in a variety of investigative and clinical studies.

Adipose Tissue↗

Changes in ovarian oestrogens and in plasma gonadotrophins in female rabbits from birth to adulthood.

Plasma oestrogens (E1, E2) and gonadotrophins, and ovarian oestrogens, were determined in female rabbits from birth to 6 months. Increases in ovarian weight followed a curvilinear pattern, with a phase of slow growth (from 1 to 60 days) preceding a phase of rapid growth (from 60 to 90 days). At birth, E2 was already quantifiable in ovaries; it remained at very low levels up to 50 days. Ovarian E2 content increased until 6 months with two sharp rises between 50 days (46 +/- 4 pg/2 ovaries) and 60 days (365 +/- 53 pg/2 ovaries) and between 80 days (326 +/- 77 pg/2 ovaries) and 90 days (1118 +/- 307 pg/2 ovaries). E1 appeared in ovaries at 50 days and then followed a pattern similar to that of E2. Oestrogens were never detected in plasma. At birth FSH and LH levels were similar to those measured in adult females but from 10 days the secretion of both gonadotrophins showed a clear dissociation. LH concentrations varied little during the period studied (between 1077 +/- 106 pg/ml to 2030 +/- 466 pg/ml). Plasma FSH levels were considerably higher between 10 and 50 days than those measured thereafter, particularly in adulthood. The decline in FSH levels occurred simultaneously with the rise in ovarian oestrogens.

Age Factors↗

Functional and morphologic characterization of human insulinomas.

Circulating levels of insulin, proinsulin-like component, glucagon, growth hormone, and pancreatic polypeptide were measured in 12 patients with functioning insulinomas, and the suppressibility of serum insulin by somatostatin and diazoxide was assessed before surgical removal of the tumors. The hormone content of the tumors was evaluated by radioimmunoassay and by immunofluorescence and the structure of the tumor cells by electron microscopy. Based on these findings, we propose a new classification of insulinomas in two groups: group A is characterized morphologically by abundant well-granulated typical B-cells, trabecular arrangement of tumor cells, and uniform insulin immunofluorescence; functionally, these tumors are associated with a moderate elevation of proinsulin-like component and with an almost complete suppressibility of serum insulin by somatostatin and diazoxide. In contrast, tumors of group B are characterized by scarce well-granulated typical B-cells, a medullary-type histologic structure, and irregular insulin immunofluorescence; functionally these tumors show elevated circulating levels of proinsulin-like component and a marked resistance of insulin secretion to somatostatin and diazoxide inhibition. This way of separating human insulinomas in groups A and B represents a simplification of existing classifications and emphasizes the quantitative ultrastructure in relationship to suppressibility of insulin secretion. The proposed classification of human insulinomas in groups A and B, however, does not allow the assessment of the clinical or histopathologic malignancy of the tumors.

Adenoma, Islet Cell↗

Sexual stimulation does not affect plasma LH nor testosterone levels in New-Zealand male rabbits.

Young sexually naive (3-4 months) and sexually experienced (2-3 years) male rabbits were subjected to various sexual stimulation procedures. Blood samples were taken just before and 30 min after mounting (unreceptive females) or coitus (receptive females). Testosterone and luteinizing hormone were assayed using specific radioimmunoassays. Sexual stimulation did not affect postcoital testosterone and LH levels in naive and experienced males while in females LH levels were significantly increased. We may conclude that the postcoital neuroendocrine reflex which causes a massive release of pituitary LH in female rabbit does not exist in males.

Animals↗

Complement receptor expression by neoplastic and normal human cells.

Complement receptor (CR) expression in cell lines derived from Burkitt's lymphoma (BL), Epstein Barr virus-transformed cord blood lymphocytes (CB), and peripheral lymphocytes from patients with infectious mononucleosis (IM) was examined. Red cell intermediates bearing various densities of C4b, C3b, C3bi, or C3d were tested for rosette formation with the cell lines. In addition, a series of studies was performed under conditions that precluded the cleavage of cellbound C3b by Factor I (C3bINA). These conditions did not alter rosetting by the cells that were tested. RAJI cells rosetted with EAC3bi greater than EAC3d greater than EAC3b, but not with EAC4b. EAC3b/RAJI rosette formation required much greater quantities of C3b bound to red cells than did CB and IM lines, which unlike RAJI, also bound EAC4b. All of the BL lines failed to bind EAC4b even at a C4b density of 50,000 molecules/cell, but several lines did form rosettes with EAC3b, and most formed rosettes with EAC3bi and EAC3d. Fluid phase C3b blocked RAJI/EAC3b rosetting while having little effect on RAJI/EAC3bi rosette activity. Moreover, fluid phase C3b, as well as C4b, blocked RAJI/EAC3b rosettes more effectively than CB/EAC3b rosettes. The results indicate that the RAJI cell line has a receptor for C3b, with characteristics that differ markedly from the C3b receptor of cell lines derived from CB lymphocytes and of lymphoblastoid cell lines derived from patients with IM. This receptor is capable of interacting with soluble but not cellbound C4b. In these studies, rosette formation was examined under various ionic conditions. RAJI/EAC3b rosette formation was severely reduced as ionic strength was increased, whereas RAJI/EAC3bi binding was only moderately decreased at physiologic ionic strength. In striking contrast, EAC3bi binding to monocytes, PMN, and human erythrocytes was markedly reduced as ionic strength increased, but EAC3b binding to these cells was less sensitive to changes in ionic strength. Under conditions of physiologic ionic strength, the C3bi receptor of phagocytic cells may be at a functional disadvantage in the binding of C3bi-coated particles. This may have major physiologic implications.

Burkitt Lymphoma↗

[Diabetes specific hand changes (cheiropathy) in children and adolescents with insulin-dependent diabetes (type I)].

215 children and adolescents with insulin dependent diabetes (age: 12(6)/12 +/- 3(9)/12 yrs; duration of diabetes 4(5)/12 +/- 3(9)/12 yrs, daily insulin requirement: 0.74 +/- 0.26 I.U./kg b.w.) were investigated for the presence of hand changes (cheiropathy) due to diabetes. Controls were 110 healthy persons of similar age (age: 11(5)/12 +/- 4(8)/12 yrs). Signs of cheiropathy were found in 44 (20.5%) of the diabetics. In 28 of these diabetics reduced mobility of the proximal and/or distal interphalangeal joints of one finger and in 16 others of at least two fingers was observed. No pathological alterations were found in the wrists, shoulder joints or spine. Mild signs of cheiropathy were seen in 5 (4.5%) of the controls. A significant positive relationship was found between age and duration of diabetes and the severity of cheiropathy. Diabetics with cheiropathy also had significantly higher daily insulin requirements than others. Of 49 patients with good diabetic control only one (2.0%) had signs of cheiropathy. In the group of 82 diabetics with fair control 12 (14.6%) showed hand changes, in the group of 84 patients with poor control 31 (36.9%). Cheiropathy must be considered to be a prognostic indicator of impending microangiopathy (retinopathy, nephropathy and neuropathy) in diabetic children and adolescents.

Adolescent↗