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Biomedical subjects

H Martin

Publications and source records attributed to H Martin.

At least 235 records · Page 13Linked to original sources

Regeneration of dystrophic muscle following multiple injections of bupivacaine.

Regenerated myofibers formed subsequent to orthotopic transplantation of young, dystrophic mouse muscle fail to display the extensive histopathological changes characteristics of murine dystrophy. In order to determine whether this modification of the phenotypic expression of murine dystrophy is unique to the transplantation system or whether it can be found when other extreme trauma induces dystrophic muscle to regenerate, the extensor digitorum longus muscles of 4-6-week-old normal (129 ReJ +/+) and dystrophic (129 ReJ dy/dy) mice were given two series of injections of the myotoxin bupivacaine, spaced 12 hours apart. These injections resulted in necrosis of approximately 90% of the original myofibers. At 100 days after injection, the regenerated normal muscle appeared "healthy," whereas the regenerated dystrophic muscle displayed histopathological changes. It is suggested that the differences in the time course of innervation of the myotubes in the transplantation system as compared with that in the bupivacaine system may be a factor in determining whether regenerated dystrophic myofibers express a dystrophic morphology.

Animals↗

Guinea pig macrophages synthesize a low molecular weight form of C1q with affinity for the C1r2C1s2-complex but which does not bind to Fc in immunoglobulin aggregates.

Biosynthetically labelled C1q secreted by guinea pig peritoneal macrophages was analysed by sedimentation through sucrose gradients followed by SDS-PAGE. In addition to the haemolytically active C1q of mol. wt 460,000 Da a low mol. wt (LMW) form of C1q was identified which had no detectable affinity for Fc of aggregated immunoglobulin, but which retained the ability to associate with the C1r2s2-complex. This LMW-C1q was covalently associated with two additional polypeptides of mol. wt 46 and 50 kDa.

Animals↗

Expert system for pathologists to generate an image analysis program for tumor grading.

The pathologist is usually not an expert in engineering or image analysis. We have, therefore, developed an expert system, entitled PARTICLE, to help pathologists producing image analysis programs by which to tackle problems in histological pathology, including tumor grading. The PARTICLE expert system is based on karyometric data, using the AMBA/R dialogue and programming system.

Diagnosis, Computer-Assisted↗

Some aspects of dexamethasone binding in the old rat liver.

The maximal glucocorticoid responsiveness and the adaptation degree are reduced in old rat liver as demonstrated by cortisol stimulation of RNA polymerases. Nevertheless the concentration of unoccupied 3H-dexamethasone binding sites in molybdate-stabilized cytosol of adrenalectomized old animals is significantly increased in comparison with young adult rats. The KD constants showed an increasing tendency, but not a significant one. In the molybdate-free cytosol the results are similar. First studies of the binding kinetics in the molybdate-free system showed a sigmoidal saturation curve in the cytosol of young adult rats, but usual hyperbolic saturation kinetics in the cytosol of old animals. The Hill coefficient was 1.0 +/- 0.1 for old and 1.9 +/- 0.3 for young animals. The binding of activated 3H-dexamethasone receptor complexes to liver nuclei showed no significant age-dependent differences in binding kinetics, acceptor site concentration or affinity. Attention must be paid to altered glucocorticoid receptor binding in the cytosol and in nuclei as a potential cause of changes in hormone-induced gene expression at the pretranscriptional level.

Aging↗

[Detection of cytokeratin in cells of the arachnoid and in meningiomas].

Only few investigations have so far become known in the context of cytokeratin expression in cells of the arachnoid and in meningioma. Immunohistochemical studies, using three monoclonal anti-cytokeratin antibodies, were conducted into six arachnoids and 43 meningiomas. Consideration was given to all histological types of meningioma but the papillary type. Three arachnoids and nine meningiomas responded positively to cytokeratin. The highest ratio of positive meningiomas, that is four in ten, was recorded from unfixed cryostat sections, using the monoclonal antibody A45-B/B3.

Arachnoid↗

Macrophage C1q: characterization of a membrane form of C1q and of multimers of C1q subunits.

It has been shown recently that C1q, a subcomponent of the first component of the classical complement pathway, is synthesized by macrophages and that endogenous C1q is detectable on the macrophage membrane. In this report, we demonstrate that membrane-associated C1q, which contains the A, B, and C chains of C1q, is structurally distinct from fluid-phase C1q in that the B chain of the membrane species is approximately 1000 m.w. less than its fluid-phase counterpart. By using biosynthetically ([3H]proline) labeled C1q from guinea pig peritoneal macrophages, we found that the membrane form of C1q is derived from already secreted C1q. The demonstration of a distinct membrane form of C1q supports earlier functional studies which implicated C1q as a membrane-associated molecule with receptor functions for those molecules which also interact with fluid-phase C1q, such as polyanions, immune complexes, and bacteria. Furthermore, we show that, in the vicinity of macrophages, C1q is very susceptible to oxidation manifested by the formation of disulfide bonds. By SDS-PAGE (nonreduced and reduced), we demonstrate the existence of disulfide-linked multimers (180,000 m.w., 360,000 m.w.) which are composed of the A, B, and C chains of C1q.

Animals↗

Combination of low-dose cytarabine and 13-cis retinoic acid in the treatment of myelodysplastic syndromes.

Responses have been reported in patients with myelodysplastic syndromes (MDS) after low-dose cytarabine (Ara-C) or 13-cis-retinoic acid (13-CRA) therapy. Recently, combination of these two substances in vitro was shown to produce a synergistic effect on differentiation of leukemic cells. We conducted a phase II trial with low-dose Ara-C (5 mg/m2 per 12 h s.c.) and 13-CRA (60 mg/m2 per day orally) in 14 patients with MDS, six of whom had refractory anemia with excess of blasts (RAEB), seven had RAEB in transformation (RAEBt) and one chronic myelomonocytic leukemia (CMML). The drugs were administered from day 1 to 14 and the treatment courses repeated every 4 to 8 weeks. One partial response and one minor response could be achieved. Major toxicity included dry skin, mucositis and cheilitis in 11 of the 14 patients. The response rate is no better than the results reported in the literature with either drugs alone. As yet there is no satisfactory treatment for MDS.

Adult↗

Morphometric and densitometric investigations of protoplasmic astrocytes and neurons in human hepatic encephalopathy.

Morphometric and densitometric evaluations were made of nuclei of astrocytes and nerve cells of 49 cases with chronic liver diseases and of 9 control cases. The data measured from Nissl-stained specimens of putamen were compared with clinical degrees of encephalopathy and with blood ammonia levels. The parameters measured included nuclear area and optical density of nuclei. The nuclear area of astrocytes (AAREA), on average, was found to grow significantly along with aggravation of encephalopathy, that growth being from 39 micron 2 in the control group to about 60 micron 2 in cases of severe encephalopathy. Furthermore the proportion of astrocyte nuclei with an area above 70 micron 2 (ALRG) and the proportion of the optical light area of the total nuclear area (AHOLE) rises. Mean compactness (ACEXT) and mean extinction of astrocyte nuclei (AMEXT) dropped along with growing severity of encephalopathy. Mean blood ammonia levels rose from 42 mumol/l in cases with no microscopically detectable signs of encephalopathy to about six times higher values in cases with severe encephalopathy. Optical density of astrocyte nuclei was negatively correlated and mean nuclear area positively correlated to blood ammonia levels. No characteristic morphometric and densitometric changes of nerve cell nuclei were recordable from the putamen.

Adolescent↗

[Significance of immunohistochemistry in neuro-oncology. V. Keratin as a marker for epithelial differentiation of primary and secondary intracranial and intraspinal tumors].

Intermediate filament keratin is regarded as a good marker for epithelial and mesothelial tumors. In the intracranial and intraspinal spaces keratin has been demonstrated only in the endocrine cells of the adenohypophysis, squamous epithelial islands in the pars tuberalis of the hypophysis and in the choroid plexus epithelium. Since gliomas and meningiomas do not express keratin, this marker provides an additional help for differentiating between primary and secondary CNS tumors. Indirect immunofluorescence using an anti-keratin serum was used in a retrospective search for keratin in 80 tumors of the cranium and intraspinal space. Of the primary CNS tumors keratin positivity occurred in craniopharyngiomas, epidermoid tumors, pituitary adenomas, chordomas, a plexus papilloma as well as in the majority of germ cell tumors. Only 3 renal cell carcinoma metastases of 21 metastatic epithelial cell tumors (7 bronchial carcinomas, 6 breast cancers, 6 renal carcinomas, 1 rectum carcinoma, 1 cervix carcinoma) were keratin-negative. Similar findings were made in two melanoma metastases which we examined, whereas in a seminoma metastasis a few keratin expressing cells were found. Primary CNS tumors such as myxopapillary ependymomas, medulloepitheliomas, malignant meningiomas and paragangliomas which are often difficult to distinguish from these metastases proved to be keratin negative.

Brain Neoplasms↗

Antibody-independent activation of the classical pathway of complement by Epstein-Barr virus.

A purified preparation of Epstein-Barr virus (EBV) has been shown to activate the classical complement pathway by direct interaction with the first component of complement, C1, without the intervention of antibody. No evidence was found for activation of the alternative pathway. Following classical pathway activation the specific affinity of EBV for B cells can be presumed to be lost since the virus will become opsonized for clearance by phagocytic cells bearing complement receptors, CR1 and CR3. This activation is further evidence that complement plays a role in defence mechanisms independently of antibody activity.

Antigens, Viral↗

Adenomyosis.

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Adult↗

[Intraneural ganglia of the common peroneal nerve].

Intraneural ganglia (pseudocysts) of the peronaeus communis nerve are rare diseases. A palpable tumour in the popliteal fossa, paraesthesia, and myasthenia, followed by sensorial and locomotor failures, are the clinical symptoms. Symptoms are mild at the beginning, which makes early detection difficult. Microsurgical extirpation of the ganglia, without touching the nerve fibres, is the therapeutic approach. Three of the authors' own cases are described in some detail.

Adolescent↗

[Supratentorially located angioblastoma in childhood. Case report].

In an 11-year-old girl an angioblastoma in a left parietal position has been successfully removed by a surgical intervention. The process consisted of a highly vascularized tumour part of a firm consistency, which was located in a large cyst. The pre-operatively established computer tomogram showed a hypodensity in the sense of a left parietal cyst and a pronounced environmental oedema. The occurrence of this tumour form in childhood and in the supratentorial section is a rarity.

Brain Neoplasms↗

[Etiology of atypical pneumonias. A serological study on 1494 patients].

In a retrospective study the serological results from 1494 patients with community-acquired pneumonia were evaluated. An infectious etiology was found in about 40% of the cases. The majority of pneumonias was caused by Mycoplasma pneumoniae and by influenza virus type A, whereas Legionella pneumophila was the fifth most frequent pathogen. In the second part of the study, 13 hospitalized patients with community-acquired pneumonia were investigated by the whole panel of routinely used microbial methods. The etiological agent was found serologically in 3 cases and in one case by cultivation. These results suggest that the determination of serum antibodies against pathogens is frequently more useful than is generally assumed, although the yield of positive results is dependent on the epidemiological situation. The detection of elevated complement-fixing titers or specific IgM antibodies often leads to diagnosis from the first serum examined.

Adolescent↗

Biosynthesis of the subcomponents C1q, C1r and C1s of the first component of complement (C1) by guinea pig hepatocyte primary cultures.

Thus far, the synthesis of C1q by liver cells has not been demonstrated. To investigate this possibility, viable hepatocytes were isolated from the liver of guinea pigs and primary cultures were established. The cells (10(6) cells/ml) were cultured under serum-free conditions for 8 days and the culture medium was changed every 24 h. The few contaminating Kupffer cells were lysed by preincubating the cell cultures with a monoclonal (22C4-8) antibody directed against a nonpolymorphic Ia determinant and preabsorbed rabbit serum. The hemolytic activity of C1 and its subcomponents C1q and C1r/C1s was tested in the supernatants. Guinea pig hepatocyte primary cultures synthesize and secrete up to 3 X 10(3) effective C1q molecules/cell/24 h and 34 X 10(3) effective C1r/C1s molecules/cell/24 h. The synthesis of C1q and C1r/C1s could be reversibly inhibited by cycloheximide (50 micrograms/ml). Furthermore, to demonstrate de novo synthesis of the C1q subcomponent, endogeneous labeling with 3H-proline (or 14C-proline) was performed. The immunoprecipitated C1q from cellular lysates and culture medium was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Compared to biosynthetically labeled guinea pig C1q from peritoneal macrophages, three corresponding bands (30, 28 and 24 kDa, respectively) were detectable in the fluorograph. The data show that guinea pig hepatocytes are able to synthesize C1 subcomponents, whereby the synthesis of C1q and C1r/C1s occurs independently.

Animals↗

Isolation and characterization of macrophage-derived C1q and its similarities to serum C1q.

Recently, we have shown that the collagen-like, Fc-recognizing subcomponent C1q of the first complement component is synthesized by human, guinea pig and mouse peritoneal macrophages. To test whether macrophages may contribute to the serum pool of C1q, C1q was purified from guinea pig serum and from guinea pig peritoneal macrophage supernatants and compared for similarities. Both molecules had a similar sedimentation rate (macrophage C1q: 11.3 S, serum C1q: 11.2 S) and showed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions three identical bands with molecular weights of Mr, 29 000, Mr, 27 000 and Mr 23 000 for the A, B and C chains, respectively. Both C1q molecules migrated by immunoelectrophoresis in the gamma region and, in Ouchterlony analysis, showed complete antigenic identity with rabbit anti-serum C1q. These experiments demonstrate the antigenic and protein chemical similarities between serum C1q and C1q secreted by macrophages supporting the idea that macrophages have to be considered as one potential source of serum C1q. Furthermore, macrophage-derived C1q may be of importance in the local microenvironment at an inflammatory site involving macrophages.

Animals↗