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Biomedical subjects

P Heimann

Publications and source records attributed to P Heimann.

At least 19 recordsLinked to original sources

Defect of sperm assembly in a neurological mutant of the mouse, wobbler (WR).

In the wobbler (WR) mouse, a neuromuscular mutant characterized by a motoneuron degeneration and male infertility, the cellular basis of the defect in spermiogenesis was studied by light and electron microscopy as well as by lectin binding. Spermatozoa of the wobbler mutant had rounded heads, and their motility was reduced. In histological sections of WR testes, spermatogenesis appeared normal up to the stage of round spermatids, but the elongation and flattening of the nucleus during late spermiogenesis did not occur. Numbers of spermatid nuclei in WR testes were reduced to 70%-80% of controls. The acrosomal marker glycoprotein, peanut agglutinin receptor, was synthesized, but the acrosomal membrane did not attach to the nucleus. The disturbance in spermiogenesis of the wobbler mouse is not due to impaired descent of the testis, nor to a lack of testosterone, and is distinct from that observed in other mouse mutants (quaking, QK; Purkinje cell degeneration, PCD) with combined neurological and spermiogenesis defects.

Acrosome

Elevated lipoprotein(a) levels in renal transplantation and hemodialysis patients.

Hyperlipidemia poses a risk for cardiovascular disease in both hemodialysis and renal transplantation patients. Although lipid profiles differ between the 2 populations, we evaluated the possibility that both groups have similar abnormalities of lipoprotein(a) [Lp(a)]. Mean serum Lp(a) and standard error of the mean (SEM) in hemodialysis and transplant recipients was 16.6 +/- 4.7 and 18.3 +/- 3.6 mg/dl, respectively, compared with 10.7 +/- 4.1 mg/dl in healthy controls, p less than 0.05. That serum Lp(a) levels are significantly elevated in dialysis and renal transplantation patients suggests at least 1 common pathogenic mechanism for the high incidence of atherosclerosis in both groups.

Adult

Monitoring free digoxin instead of total digoxin in patients with congestive heart failure and high concentrations of digoxin-like immunoreactive substances.

Digoxin-like immunoreactive substances (DLIS) are present in patients with conditions associated with volume expansion (including hypervolemic hypertension, renal failure, and liver failure) and in pre-eclampsia and premature birth. These strongly-protein-bound substances cross-react with anti-digoxin antibodies and cause falsely increased measured concentrations of digoxin in serum. Patients with congestive heart failure (CHF) often have volume expansion and are receiving digoxin therapy. They are also very sensitive to digoxin toxicity and have a very narrow therapeutic range (1.0-1.9 nmol/L). We found monitoring the concentrations of free digoxin (in protein-free ultrafiltrates) helpful in eliminating the interferences of DLIS in CHF patients. DLIS concentrations were measured by fluorescence polarization assay. Concentrations of DLIS were detectable in significantly more (58.3%) of the 12 CHF patients (group A) who were not receiving digoxin than in the 22 normal volunteers tested (13.6%) (P less than 0.05 by both chi-square and Fisher's exact test). Protein-free filtrates from patients or normal volunteers did not show any measurable DLIS activities. We also determined the concentrations of total and free digoxin in 12 patients with CHF who were receiving digoxin (group B) and compared the results with those for 22 patients receiving digoxin without the diagnosis of CHF or any known pathological conditions that could increase DLIS concentrations. The ratio of free to total digoxin in patients in group B was significantly lower (mean = 52.8%, SD 10.2%) than in those receiving digoxin (mean = 72.7%, SD 6.5%) for other reasons (independent two-tailed t-test, P less than 0.05).

Digoxin

Tissue specific distribution of calcyclin--10.5 kDa Ca2+-binding protein.

Expression of calcyclin in different cell lines and mouse tissues was determined with polyclonal antibodies raised against calcyclin from Ehrlich ascites tumour (EAT) cells. The protein was detected in mouse skeletal and cardiac muscle, in lung, kidney and spleen, and was especially enriched in mouse smooth muscle as well as in rat fibroblasts. No positive immunological reaction was detected in mouse brain, liver and intestine and some tumourigenic cell lines. The level of calcyclin mRNA found in different cells and tissues corresponded well to the calcyclin level estimated by immunoblotting. The calcyclin-like protein was purified from mouse stomach and appeared to be very similar to the EAT protein.

Animals

Interaction of polymorphonuclear leukocytes with cartilage in vitro. Catabolic effects of serine proteases and oxygen radicals.

The ability of purified PMN serine proteases as well as oxygen-derived free radicals (ODFR) generated by activated phagocytes to damage cartilage matrix has been thoroughly investigated in vitro. The question in the present study was the extent to which enzymatic and ODFR-mediated mechanisms can contribute to the degradation of bovine cartilage slices by zymosan-stimulated PMN. Tissue destruction as assessed by mechanical parameters of stability as well as by liberation of uronic acids from matrix proteoglycans was not inhibitable by the radical scavengers superoxide dismutase (SOD) and catalase (CAT), while serine protease inhibitors led to a significant reduction of matrix degradation. Thus an enzymatic mechanism may play a major part in PMN-induced cartilage damage. Besides this predominant role of especially serine proteases a direct, non-zymosan-dependent stimulatory effect of cartilage matrix on PMN to release elastase into the incubation medium was detected. Hence an as-yet unknown mechanism of PMN activation is indicated, while unspecific effects by bacterial contamination, complement factors, or endotoxin could be excluded as an explanation for the observed phenomenon.

Animals

Dolichos biflorus agglutinin receptors in mouse muscle. I. Developmental expression in relation to synaptic acetylcholinesterase and to neuromuscular disease.

The lectin (agglutinin) from Dolichos biflorus (DBA) binds selectively to the neuromuscular junction of different vertebrate species. We have examined the synaptic DBA receptors in skeletal muscle during postnatal development and in neuromuscular diseases of the mouse. No DBA binding was found at neuromuscular junctions of muscles from newborn mice, when acetylcholine receptors and acetylcholinesterases were already concentrated at the endplate. Synaptic accumulation of DBA receptors was evident 4 days after birth, and the staining intensity increased until postnatal day 10 to 12 when it reached the adult level. As shown by ultrastructural histochemistry, accessible DBA binding sites were confined to the crests of junctional folds in motor endplates of 4-day-old mice, whereas adult endplates exhibited DBA binding sites in the entire synaptic cleft including the junctional folds. Two neuromuscular hereditary diseases of the mouse, 'wobbler' (WR) and 'motor endplate disease' (MED) were examined. At the light microscopic level, DBA binding was normal in WR and MED endplates. At the ultrastructural level, MED synapses showed reduced junctional folds but unaffected DBA binding capacity.

Acetylcholinesterase

Increased density of satellite cells in the absence of fibre degeneration in muscle of myotonic mice.

A mutant mouse with a hereditary myotonia, 'arrested development of righting response', ADR, was investigated with respect to mononucleated cell populations in skeletal muscle. Upon enzymatic dissociation of different muscles from mice aged between 15 and 120 days, a 3- to 5-fold higher yield of mononucleated cells per muscle fresh weight was obtained from mice with the ADR syndrome than from control mice. Clonal cell culture showed that the absolute number of cells with myogenic potential was increased and that mutant clones had shorter generation times than wild-type controls. Morphological differentiation of ADR myotubes was indistinguishable from that of the controls. Light microscopy confirmed the presence of increased numbers of mononucleated cells per muscle volume. At the ultrastructural level, there were 3.3 times as many satellite cells (the myogenic stem cells of mature muscle) per myofibre nucleus in ADR than in controls. Because no fibre degeneration was observed in the ADR mutant, we conclude that the enlarged mutant satellite cell pool is not a result of compensatory proliferation but is a consequence of fibre-type transformation and/or delayed maturation of the myotonic muscle.

Aging

Fine structure of sensory tubes on the antennule of Conchoecia spinirostris (Ostracoda, Crustacea). A new type of sensillum in crustaceans.

In addition to setae, the first antennae of Conchoecia spinirostris also bear soft sensory tubes (female: 4 tubes + 1 seta; male: 2 tubes + 3 setae). These tubes were examined electron microscopically. Each tube is divided into 4 regions: the stem, the bulbous region, the main region, and the tip. A tube contains 40--60 multiciliated dendrites, some hypodermal cells, and nonneuronal cells, and it has a specialized cuticle. Each dendrite develops within the tube, on the terminal 5--8 micron of its inner dendritic segment, approx. 25 cilia in a 9 X 2 + 0 pattern, whose rootlets are absent or only poorly developed. Each cilium splits up into 9 ramifications which extend into the tip. These ramifications partly take a spirallike course and form a ring in the distal main part beneath the cuticle. Their membranes often dilate into spindleshaped swellings. In the center of the middle and distal parts of the main region approx. 7 dendrites without cilia are located, one of them reaches into the tip. The poreless cuticle is extremely delicate and electron lucid. In contrast to the cuticle of the setae it is elastic and soft. Special substructures are described. The tubes are completely covered by a filamentous surface coat. Because of the structure and the thin walled nature of the cuticle, permeability for dissolved substances is assumed. The ciliary ramifications are likely to represent the receptive apparatus. The sensory tubes are interpreted as chemoreceptors. They can best be compared with the chemoreceptors of certain crustaceans, but differ strongly from the types of sensilla found in insects.

Animals

Lymphocyte subpopulations in thymus and blood from patients with myasthenia gravis.

Cell suspensions were prepared from hyperplastic thymic tissue and lymphoepithelioma from patients with myasthenia gravis and from presumed normal thymic tissue obtained at cardiac surgery. The mononuclear cells were examined for surface markers. The mean percentages of both T lymphocytes and Fc receptor-carrying lymphocytes were similar in the three groups, whereas there was an increase in C receptor-carrying lymphocytes in the samples from myasthenic patients. Sections from the thymus gland were examined for T and B markers. In the hyperplastic thymus and in lymphoepithelioma, the T lymphocytes were distributed diffusely throughout the cortex and the medulla; in the normal thymus they were predominant in the cortex. The mean percentage of T and B lymphocytes in peripheral blood from patients with myasthenia gravis was normal. Thymectomy involved a transitory decrease in T lymphocytes with a corresponding increase in B lymphocytes.

B-Lymphocytes

Development of sequence specific radioimmunoassay of human parathyroid hormone and its use in the diagnosis of hyperparathyroidism.

Two antisera which were raised against bovine parathyroid hormone (bPTH), and which cross-reacted with the human hormone, have been characterized. The antisera which originated from rooster and guinea-pig, were found to contain several populations of antibodies directed against both N-terminal and C-terminal sequences of the hormone. However, at proper dilutions the rooster antiserum did not bind the N-terminal fragment nor could this fragment displace the [125I] bPTH (1--84 amino acid residue) from binding to the antiserum. Furthermore, preincubation experiments with excess N-terminal fragment showed only a negligible reduction in maximal binding of the iodinated intact hormone using the rooster antiserum. In contrast, the guinea-pig antiserum reacted equally well with the N-terminal fragment and the intact hormone, and preincubation with this fragment reduced the binding of the [125I]bPTH (1--84 amino acid residues) by 75%. Gel filtration of hyperparathyroid serum on Bio-Gel P-60 showed immunoreactive material which was measured with both antisera, eluting at a position similar to the intact hormone. However, in the C-terminal specific, but not in the N-terminal specific radioimmunoassay the major component eluted together with or somewhat earlier than the N-terminal bPTH fragment (1--34 amino acid residue), and this peak represented more than 90% of total immunoreactive PTH (iPTH) in serum. This major iPTH component must therefore represent fragment(s) with intact carboxy-terminal sequences. The N-terminal specific radioimmunoassay was unable to measure iPTH in about 80--90% of healthy individuals while the C-terminal specific assay detected iPTH in about 88% of these sera (equal to or above 0.1 micrograms/l). Similarly, the N-terminal specific antiserum measured consistently lower serum iPTH concentrations in patients with primary hyperparathyroidism. In thirty-four out of forty-one patients with surgically verified primary hyperparathyroidism, serum iPTH concentrations equal to or above 0.60 micrograms/l were demonstrated using the C-terminal, specific radioimmunoassay.

Acute Disease

Thyroid carcinoma: diagnosis and treatment in 106 patients.

106 patients with a primary thyroid cancer treated in the years 1971--1977 have been studied with respect to preoperative diagnosis and to treatment. We can demonstrate an improved diagnostic accuracy during the 7-year period. Aspiration fine needle biopsy with cytological examination was the preoperative diagnostic method which gave the highest yield. Total thyroidectomy, preferably as a one-stage procedure has been performed in 77 patients.

Adenocarcinoma