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Biomedical subjects

W Muller

Publications and source records attributed to W Muller.

At least 55 records · Page 3Linked to original sources

Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo.

We have derived and mated separate strains of transgenic mice that carry either the v-Ha-ras or the c-myc gene driven by the mouse mammary tumor virus (MMTV) promoter/enhancer. Mice carrying the MMTV/v-Ha-ras transgene manifest two distinct disturbances of cell growth. The first, a benign hyperplasia of the Harderian lacrimal gland, is diffuse, involves the entire gland, and likely requires only the abnormal action of the v-Ha-ras gene. The second involves the focal development of malignancies of mammary, salivary, and lymphoid tissue and likely requires additional somatic events. When the MMTV/v-Ha-ras and MMTV/c-myc strains are crossed to yield hybrid mice, their joint action results in a dramatic and synergistic acceleration of tumor formation. Since these tumors arise stochastically and are apparently monoclonal in origin, additional somatic events appear necessary for their full malignant progression, even in the presence of activated v-Ha-ras and c-myc transgenes.

Adenocarcinoma↗

Ciclosporin and prednisone v. prednisone in treatment of Graves' ophthalmopathy: a controlled, randomized and prospective study.

Forty patients with Graves' ophthalmopathy stages III-V were divided into two groups in a random manner according to their year of birth. Group I received prednisone in decreasing dosage. Group II received prednisone at a comparable dosage and ciclosporin. Steroids were discontinued after 10 weeks in the two groups. In the patients of group II, ciclosporin was continued over 12 months. The therapeutic effect was assessed by an activity score based on subjective and objective symptoms (computerized tomography and sonography of the orbit, Hertel values, clinical findings). All signs of endocrine ophthalmopathy improved significantly in both groups (P less than 0.01 in group I; P less than 0.001 in group II). The improvement was significantly greater in group II (P less than 0.05) according to the predefined score. After corticosteroids were discontinued, inflammatory signs recurred in nine patients in group I and in one of group II. During the observation period of 12 months, relapses occurred in eight out of twenty patients in group I and in only one out of twenty in group II. Muscle thickness decreased in nine patients in group II, 6 months after beginning therapy. At this time, the results were not influenced in any of the twenty patients in group I. Microsomal antibodies decreased significantly (P less than 0.001) in the ciclosporin group, whereas no change was seen in the other group. Renal values rose within the normal range in group II. In this group, an infection with Klebsiella pneumoniae occurred in one patient after 4 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The contused kidney, an angiographic picture.

Problems in the interpretation of an angiogram of a contused kidney are reported. The angiogram showed signs of avascularity and tumor vessels and a malignancy was considered. However, on operation the kidney appeared to be contused but otherwise normal. One should be aware of the possibility of pitfalls arising in early angiograms of contused kidneys.

Adult↗

HZE effects on mammalian cells.

In track segment experiments cell survival and chromosome aberrations of mammalian cells have been measured for various heavy ion beams between helium and uranium in the energy range between 0.5 and 960 MeV/u, corresponding to a velocity range of 0.03 to 0.87 C, and an LET spectrum from 10 to 15 000 keV/micrometers. At low LET, the cross section (sigma) for cell killing increases with increasing LET and shows a common curve for all ions regardless of the atomic number. This indicates that in this region the track structure of the different ions is of only a minor influence, and it is rather the total energy transfer, which is important for cell killing. At higher LET values, deviations from a common sigma-LET curve can be observed which indicate a saturation effect. The saturation of the lighter ions occurs at lower LET values than for the heavier ions. These findings are also confirmed by the chromosome data, where the efficiency for the induction of chromosomal aberrations for high LET particles depends on the track structure and is nearly independent of LET. In the heavier beams (Z > or = 10) individual particles cause multiple chromosome breaks in mitotic cells.

Animals↗

Increased frequency of HLA B8 in hyperostotic spondylosis.

HLA antigens were determined in 50 patients with hyperostotic spondylosis (Forestier's disease), and compared with 1244 normal controls. There was no significant difference in the distribution of HLA B27 between the two groups. However, there was an increased incidence of HLA B8 among the patients with hyperostotic spondylosis (42 per cent), as compared to the normal controls (17.5 per cent). This difference was statistically significant (p less than 0.005). Sixteen of the 50 patients with hyperostotic spondylosis had evidence of diabetes mellitus, 12 of whom also had the HLA B8 antigen. Thus patients with hyperostotic spondylosis have an increased incidence of HLA B8, associated with an increased incidence of diabetes mellitus.

Diabetes Complications↗

The effect of levamisole on adjuvant arthritis in the rat.

Levamisole (LEV), an immunostimulatory agent, was studied for its effect on adjuvant disease of the rat. The drug was administered continuously according to three schedules: (a) seven days prior to immunization with complete Freund's adjuvant (CFA); (b) simultaneously with CFA; or (c) 14 days after CFA. Control animals received CFA alone, LEV alone, or were sham treated with saline. Three weekly evaluations were made, recording the general condition, weight curves, joint scores, and volume of hind paws. Whole body radiographs were made at the end of six weeks. In all experimental groups, LEV accentuated the severity of the disease as compared to animals receiving CFA alone. Within the experimental groups, an increased severity was observed with earlier administration of LEV, although the day of disease onset was not altered. Spinal involvement was less severe with each consecutive administration of LEV. These findings suggest that LEV is effective not only in restoring an impaired cellular immune response, but also in enhancing an already activated system. It seems however, that for this stimulation the timetable of LEV administration is crucial, and that continuous therapy may result in a loss of efficiency.

Animals↗

Lymphocyte subpopulations in normals and patients with rheumatoid arthritis and ankylosing spondylitis.

Seventy-four normal persons, 48 patients with rheumatoid arthritis, and 25 patients with ankylosing spondylitis, were examined in respect to lymphocyte subpopulations in the peripheral blood. The simultaneous enumeration of T lymphocytes (E rosettes), B lymphocytes (surface immunoglobulin), as well as null cells and double marker cells was performed. No significant differences could be observed in the three examined groups in respect to the absolute or the relative lymphocyte counts, suggesting that possible immunological impairment assumed in rheumatoid arthritis and ankylosing spondylitis, is due not to reduced cell numbers, but to a possible functional disorder.

Arthritis, Rheumatoid↗

Orientation of silk III at the air-water interface.

A threefold helical crystal structure of Bombyx mori silk fibroin has been observed in films prepared from aqueous silk fibroin solutions using the Langmuir Blodgett (LB) technique. The films were studied using a combination of transmission electron microscopy and electron diffraction techniques. Films prepared at a surface pressure of 16.7 mN/m have a uniaxially oriented crystalline texture, with the helical axis oriented perpendicular to the plane of the LB film. Films obtained from the air-water interface without compression have a different orientation, with the helical axes lying roughly in the plane of the film. In both cases the d-spacings observed in electron diffraction are the same and match a threefold helical model crystal structure, silk III, described in previous publications. Differences in the relative intensities of the observed reflections in both types of oriented samples, as compared to unoriented samples, allows estimations of orientation distributions and the calculations of orientation parameters. The orientation of the fibroin chain axis in the plane of the interfacial film for uncompressed samples is consistent with the amphiphilic behavior previously postulated to drive the formation of the threefold helical silk III conformation.

Air↗

The presence of HLA-DR B1 shared motif does not influence cyclophosphamide and methotrexate cytotoxicity in rheumatoid arthritis patients.

In the present study we investigated the relation between cyclophosphamide and methotrexate toxicity and the presence of HLA- DR B1 alleles in rheumatoid arthritis patients. Seventy-eight such patients (67 women and 11 men) were observed for 12 months. Eighteen were treated with intravenous cyclophosphamide, 28 with oral methotrexate, and 32 with intramuscular gold salts. The prevalence of this shared motif was higher in the study population than in the healthy controls. However, detailed observations did not demonstrate a relation between particular genotype and drug intolerance. Based on the obtained findings we concluded that HLA-DR B1 typing cannot affect cyclophosphamide or methotrexate tolerance in rheumatoid arthritis patients. However, taking into account the relatively small number of patients expressing single genotype, further studies are recommended.

Adult↗

Does the presence of HLA-DR B1 shared motif affect progression of the disease in rheumatoid arthritis patients?

The present study was undertaken in order to evaluate role of HLA DR Bl shared motif in prognosis of development of erosions in rheumatoid arthritis (RA). HLA genotyping was carried out in a retrospective analysis of 73 RA patients and 87 healthy controls using polymerase chain reaction. The assessment of disease activity was performed according to Mallya-Mace Index, whereas radiographs of hands were assessed according to the Larsen Index. HLA-DR4 and DR10 were significantly increased among RA patients. Relative risk was 7.540 and 4.646, respectively. Interestingly, the presence of DRl and DR14 did not enhance the relative risk in our group of patients. Determination of HLA-DR B1 alleles showed that among RA patients the most frequent was HLA-DR Bl*0401, *0404, and *0408. They gave a rise to a relative risk of 4.010, 7.540, and 3.686 respectively. For the purpose of analysis the patients were divided into three groups. The first group comprised 14 patients with two high-risk alleles (HLA DR B1 *01, *0401, *0404, *0408, *14). The second group gathered 35 patients with one high-risk allele. Twenty-four patients with no high-risk alleles were designated to the third group. We did not notice any differences in damage score and progression of damage score in rheumatoid arthritis patients with different number of high risk motifs. In conclusion, HLA-DR B1 shared motif was found to be significantly more frequent among analyzed erosive rheumatoid arthritis as compared to matched healthy controls. We did not observe any relation between the presence of shared motifs and outcome of the disease. Therefore, it seems that HLA DR B1 determination may very helpful in diagnosing or in establishing groups of risk but it is not likely to have a role in predicting development aggressive forms of RA.

Journal Article↗

Cholinergic and noradrenergic neurotransmission: impact on REM sleep regulation in healthy subjects and depressed patients.

The reciprocal interaction model of NonREM- and REM sleep regulation suggests that the cycling alternating pattern of Non-REM- and REM sleep is under the control of noradrenergic/serotonergic and cholinergic neuronal networks. This model was tested in healthy humans by administration of cholinergic agonists/antagonists and noradrenergic antagonists prior to or during sleep. Cholinomimetics like physostigmine, RS 86 and galanthamine provoked an earlier onset of REM sleep, whereas subchronic treatment with scopolamine, a cholinergic antagonist, only led to a heightening of REM density. Simultaneous administration of noradrenergic antagonists with a cholinergic agonist did not provoke a more pronounced REM sleep advance. Comparative studies with the cholinergic agonist RS 86 in depressed patients, schizophrenic patients and patients with other psychiatric disorders revealed the most pronounced REM sleep response in the depressed group. The REM sleep response to cholinergic stimulation in depression did however not predict the treatment response to a differential-therapeutic strategy.

Adolescent↗

Seven cases of testicular tumors with two cryptorchidism.

Seven patients with testicular tumor were reviewed. Among them were two patients with cryptorchidism which had not been suspected. All were treated with orchidectomy through an inguinal incision or by laparotomy. Afterwards the seminomata underwent radiation therapy, and in the malignant teratoma intermediate, when ever possible, a retroperitoneal lymphnode dissection was done. The malignant teratoma undifferentiated (stage IV) received chemotherapy (cis-diamminodichloroplatinum) with good results. The lymphoblastic sarcoma (stage IV) was treated with methotrexate and vincristine. It is suggested that in patients with cryptorchidism the undescended or intra-abdominal testis should always be explored, and excised if suspect or underdeveloped.

Adolescent↗

Acute-phase response in early refractory rheumatoid arthritis: long-term follow-up study.

In order to investigate the role of the acute-phase response in early rheumatoid arthritis (RA), we followed the changes of alpha 1-acid glycoprotein (AGP), alpha 1-antitrypsin (AT) and alpha 1-antichymotrypsin (ACT) in the sera of 25 patients with refractory rheumatoid arthritis (RA) during the first 3 years of the disease. Serum levels of AGP, ACT and AT were measured using rocket immunoelectrophoresis, and AGP, ACT and AT microheterogeneities were performed using two-dimensional immunoelectrophoresis with concanavalin A (Con A) as ligand. On average, serum levels of AGP, ACT and AT proteins were higher at the onset of the disease as compared with healthy controls. After 3 years, a significant decrease in serum levels of all three acute-phase proteins (APPs) was observed, but only in patients without anatomical progression was this decrease statistically significant. At the beginning of the study, only the AT reactivity coefficient (RC) was decreased in comparison with healthy subjects. However, after 3 years of disease, AGP, ACT and AT RCs all decreased. This investigation provided two new observations. The first is that only AT RC is significantly lower in comparison with normal values at the beginning of RA, whereas AGP RC and ACT RC remain within the normal range of values; a decrease in AGP RC and ACT RC appeared later. The second observation is that the highly elevated levels of APPs at the onset of RA decrease during the course of the disease. Moreover, this decrease does not depend on the disease activity, but a relationship with radiological progression was shown.

Acute-Phase Proteins↗

Does IgA-alpha1 antitrypsin complex correlate with IgM, IgG and IgA rheumatoid factor in early rheumatoid arthritis?

This study was undertaken to determine whether the rheumatoid factor (RF) isotypes affect the level of IgA-AT complex in early rheumatoid arthritis. IgA-AT complex and IgM, IgG, and IgA RF were evaluated using a double antibody enzyme-linked immunosorbent assay (ELISA) in sera of 83 (61 women and 22 men) patients. The mean level of the complex was higher in RA patients as compared with the control group (0.60 +/- 0.41 U vs 0.19 +/- 0.11 U, p < 0.05). The IgA-AT complex values exceeding the norm were found in 19 of 83 RA cases (23%), mainly in patients non-treated with DMARDs. IgM RF values judged as positive were present in 53 (64%), IgG RF in 55 (66%), and IgA RF in 56 (67%) patients. Higher RF values of IgM and IgG, but not those of IgA class, were found more frequently in patients with elevated IgA-AT levels. A good correlation was established between IgA and IgM RF (r = 0.61, p < 0.01), but not between IgA and IgG, or IgM and IgG RF in the group of patients under study. However, we did not find any significant correlation between isotypes of RF and parameters of the disease activity.

Adult↗