Biomedical subjects
Publications and source records attributed to M Huber.
This case report describes a right coronary artery arising from the ascending aorta, above the left posterior sinus. Unlike previously reported cases, this was associated with a normal aortic valve. The clinical significance and approach during angiography are discussed.
A case of pelviscopic hysterectomy with uterine hyperflexion and cervical elongation is presented. In this case we were forced to extirpate the cervical fascia because of uterine hemorrhage by laparotomy after the cervical tissue punch had been performed. The histological findings were supravaginal cervical glands. Complete removal of cervical glandular tissue may be undetermined by hyperflected uteri and cervical elongation.
We studied the fixation of a cementless titanium femoral prosthesis partially coated with hydroxyapatite ceramic (HAC) 10.4 months after implantation. Histomorphological investigation showed extensive new bone formation between the HAC coating and the bone bed; morphometry showed bone contact indices of up to 91.60%. There were a number of resorption lacunae on the HAC coat with depths of up to 76.6 microns and widths of up to 453 microns. Our results confirmed that considerable bone remodelling had taken place and that the apatite-coated prosthesis had united with bone despite the lack of appreciable immediate press-fit. Hydroxyapatite particles which had been released did not appear to show any negative effects on the stability of the implant.
UNLABELLED: The mannose transporter of the bacterial phosphotransferase system consists of two transmembrane subunits (IICMan and IIDMan) and a hydrophilic subunit (IIABMan). IIABMan has two flexibly linked domains containing one phosphorylation site each and occurs as a dimer. Substrate transport is coupled to phosphorylation. The phosphoryl group is transferred from a phosphoryl carrier protein to His10 on IIA, hence to His175 on IIB and finally to the substrate. IIABMan mutants were analyzed in vitro for complementation, negative dominance, cysteine cross-linking and reactivity. CONCLUSIONS: (i) His10, Trp12, Lys48, and Ser72 form a functional unit (phosphorylation site 1); (ii) His86 on the IIA domain and His175 on the IIB domain of the same subunit form a functional unit (phosphorylation site 2); (iii) phosphoryl transfer can occur between His10 and His175 of the same as well as of different subunits and His86 is necessary for this transfer; (iv) the subunits in the dimer are interdependent; (v) The phosphorylation site mutant H175C is highly reactive toward thiol reagents and it forms extensive homo- and heterocross-links with other surface-exposed cysteines. The phosphorylation site mutant H10C is 1000-fold less reactive. The two residues might be in complementary locations, His10 buried in a concave, His175 exposed on a convex surface.
In a patient with acute posterior multifocal placoid pigment epitheliopathy (APMPPE), a pontine infarction occurred about 6 months after the ophthalmological manifestation. We report the first case with histopathologically proven vasculitis shown by muscle biopsy and the first positron emission tomographic documentation in APMPPE. The ophthalmological and cerebral symptoms responded well to steroid treatment. Long-term immunosuppression (e.g. azathioprine 1-2 mg/kg) seems to decrease the risk of recurrent systemic vasculitis.
This study examined whether longer duration on nicotine gum promoted dependence on nicotine gum. Subjects (N = 128) answering an advertisement for smoking cessation research and wanting to quit smoking cigarettes were randomly assigned to 1- or 3-month duration of nicotine gum use. Assessments were made weekly for smoking status (with biochemical verification) and withdrawal symptoms during and at the end of treatment. Follow-up was conducted at 1, 6 and 12 months to provide exploratory data on treatment outcome. The results showed minimal nicotine gum withdrawal symptoms after gum cessation with virtually no difference in gum withdrawal between the 1- and 3-month groups. Withdrawal symptoms from the nicotine gum included difficulty with concentration, increased variability on a reaction time task, and decreased vigor. The results also showed that continuous use of the gum at 1 year was observed in 1.5% of subjects and estimated to be as high as 14%. Finally, the 3-month group experienced a 2-fold increase in abstinence compared to the 1-month group, although this difference was not statistically significant. We conclude that there is minimal physical dependence on nicotine gum.
In a randomized double-blind placebo-controlled study in 30 patients with acute ischemic stroke, the effect of the adenosine uptake blocker propentofylline on regional brain glucose metabolism (rCMRglu) was investigated using repeated positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG). Treatment was initiated within 48 h after onset of symptoms. The clinical course was followed for 3 months. In the propentofylline group, after 14 days rCMRglu was increased in the infarct by 37.3% and was practically unchanged in other brain regions, whereas in the control group glucose metabolism had decreased in all regions (1.4-13.4%). These differences were significant between the two groups [Analysis of variance (ANOVA) p = 0.005]. Although there was a trend toward greater clinical improvement in the propentofylline-treated patients, this did not reach statistical significance. The results correspond to experimental data showing that propentofylline improves energy metabolism in cerebral ischemia. A clinical trial is needed to determine whether this new therapeutic principle can be successfully used in acute human stroke.
Epidermolytic hyperkeratosis (EHK), (bullous congenital ichthyosiform erythroderma), is an autosomal dominant human skin disorder. Recently, we and others have described mutations in keratins 1 and 10 (K1 and K10) in patients with this disease. Structure-function models predict that these mutations would impair normal filament assembly and function. We have extended our earlier studies to include 8 more incidences of EHK. In half of these families, we were unable to locate a mutation within the rod domains of either K1 or K10. However, polymorphic restriction site and sequence analysis of the other families revealed a mutational hot spot within the 1A alpha-helical segment of K10. These involve Arginine to Histidine, Arginine to Cysteine and Arginine to Leucine substitutions at residue 10 of the rod domain. Interestingly, mutations in the corresponding Arginine residue in keratin K14 have been identified in patients with epidermolysis bullosa simplex. The large number of mutations found at this position in both keratins K10 and K14 suggests that other epithelia cell disorders will be discovered that are caused by the corresponding mutation in related type I keratin genes.
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In this study we analyzed the expression patterns of loricrin in various species and tissues using immunohistochemistry, immunoblotting and Northern blots. Loricrin is a glycine-, serine- and cysteine-rich protein expressed very late in epidermal differentiation in the granular layers of normal mouse and human epidermis. Later on in differentiation, loricrin becomes crosslinked as a major component into the cornified cell envelope by the formation of N epsilon-(gamma-glutamyl)lysine isopeptide bonds. This process either occurs directly or by the intermediate accumulation in L-keratohyaline granules of mouse epidermis and human acrosyringia. Loricrin was identified in all mammalian species analyzed by virtue of its highly conserved carboxy-terminal sequences revealing an electric mobility of approximately 60 kDa in rodents, rabbit and cow and of approximately 35 kDa in lamb and human on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Loricrin is expressed in the granular layer of all mammalian orthokeratinizing epithelia tested including oral, esophageal and fore-stomach mucosa of rodents, tracheal squamous metaplasia of vitamin A deficient hamster and estrogen induced squamous vaginal epithelium of ovary ectomized rats. Loricrin is also expressed in a few parakeratinizing epithelia such as BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine]-induced murine bladder carcinoma and a restricted subset of oral and single vaginal epithelial cells in higher mammals. Our results provide further evidence that the program of squamous differentiation in internal epithelia of the upper alimentary tract in rodents and higher mammals differ remarkably. In addition, we also have noted the distinct distribution patterns of human loricrin and involucrin, another major precursor protein of the cornified cell envelope.
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BACKGROUND: Loricrin and involucrin are major precursor proteins to the cornified cell envelope expressed late in epidermal differentiation. Involucrin expression starts in the upper spinous layers in normal human epidermis and precedes loricrin expression, which is restricted to the granular layer. Subsequently, both proteins become cross-linked by the activity of transglutaminases TGK/E as major components of the cornified cell envelope by N epsilon-(gamma-glutamyl)lysine isopeptide bonds. In this study, three cases of lamellar ichthyosis were analyzed by immunohistologic study with antibodies to loricrin, involucrin, filaggrin, and transglutaminase TGK. OBSERVATIONS: A high expression of loricrin and involucrin with a peculiar and abnormal cytoplasmic staining concurred with a diminished cytoplasmic staining of transglutaminase TGK as assessed by antibodies B.C.1 and K.D.3. This pattern was absent in a collodion baby at birth but present 2 weeks later before a phenotype of lamellar ichthyosis appeared clinically. CONCLUSIONS: The results suggest that in our cases of lamellar ichthyosis, (1) disturbed membrane anchorage of transglutaminase TGK could alter loricrin and involucrin cross-linkage and the formation of the cornified cell envelope and that (2) immunohistologic study might serve as an early diagnostic and prognostic tool in the treatment of collodion babies.
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Epidermolytic hyperkeratosis is a hereditary skin disorder characterized by blistering and a marked thickening of the stratum corneum. In one family, affected individuals exhibited a mutation in the highly conserved carboxyl terminal of the rod domain of keratin 1. In two other families, affected individuals had mutations in the highly conserved amino terminal of the rod domain of keratin 10. Structural analysis of these mutations predicts that heterodimer formation would be unaffected, although filament assembly and elongation would be severely compromised. These data imply that an intact keratin intermediate filament network is required for the maintenance of both cellular and tissue integrity.
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Asp-208 of Streptomyces glaucescens tyrosinase (an invariant residue in the CuB-binding region of tyrosinases and haemocyanins) was conservatively substituted by glutamic acid. Although having little effect on spectroscopic or kinetic properties of the enzyme, the mutation greatly decreased the lability of Cu-bound O2. A rationalization for these results is given, based on the crystal structure of Panuliris interruptus haemocyanin in the conserved CuB-binding region.
18FDG-positron emission tomography performed at different stages in the course of subacute sclerosing panencephalitis revealed a changing pattern of metabolic disturbance. In clinical stage II patients the inflammation in the basal ganglia appeared to lead to neuronal excitation accompanied by hypermetabolism. Widespread cortical functional inhibition of metabolism followed. The striatal inflammation ended with necrosis and hypometabolism, with resulting functional cortical disinhibition; later, deep midbrain structures and brain stem became hypermetabolic. A patient clinically in remission showed no such changes in cerebral glucose metabolism.