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Biomedical subjects

C Sartorius

Publications and source records attributed to C Sartorius.

At least 19 recordsLinked to original sources

[Salivary duct carcinoma of the sublingual gland--a case report].

RATIONALE: Pleomorphic adenoma is the most common neoplasm of major and minor salivary gland origin, followed by infectious reasons and sialolithiasis. Less common are adenocarcinomas presented. The salivary duct carcinoma represents a rare variant of the group of adenocarcinomas originated from the salivary glands, especially extremely rare from minor salivary gland origin. CASE REPORT: We report about a 52 year old male patient presenting with painless, non-ulcerating tumor at the floor of the mouth. Since 2 weeks ingestion was painful. Further ENT-investigations including endoscopy and scans (MRT, ultrasound) showed no pathology. In particular, growth of cervical lymph nodes and distant metastases were not revealed. A biopsy showed a rare salivary duct carcinoma of comedo-type originated from the left sublingual salivary gland. The patient underwent an operation: the tumor was extirpated in toto, and, as the pathohistological investigation confirmed, in sano. Additionally a neck dissection at the left side was performed, followed by the radiation of the tumor region and the lymphatic neck regions, after sufficient reconvalescence. The tumor-classification was pT3, pN0. Since 3 years no recurrence of the tumor was confirmed. DISCUSSION: Salivary duct carcinoma is a rare, high-grade malignant epithelial neoplasm, which occurs almost exclusively in the parotid. As presented, it can also occur in minor salivary glands. Histologically it is composed of structures that resemble expanded salivary glands. Comedonecrosis of these structures is a frequent feature. There is some histologic similarity to intraductal carcinoma of the breast. Differential diagnosis comprises adenoid cystic carcinoma, metastases of other adenocarcinomas, such as the carcinoma of the thyroid gland and the comedocarcinoma of the breast. Because of its poor prognosis a rapid and radical therapy is recommended. CONCLUSION: A rare case of a salivary duct carcinoma of sublingual salivary gland origin is presented. Usually the prognosis is poor. The adequate therapy is the complete surgical extirpation including the surgery of the regional lymphatic nodes and the additional radiotherapy.

Biopsy↗

[Granular cell tumor -- a rare tumor lesion of submandibular gland origin].

RATIONALE: Granular cell tumors are rare entities with manifestations in nearly all organ systems. Appearance in salivary glands is observed in singular cases. CASE REPORT: We report a 54 years old female patient with a painless submandibular tumor lesion. Using a submandibular approach the tumor was totally removed with the submandibular gland. Histologically a benign granular cell tumor was diagnosed. The immunohistological examination revealed positive for S-100 antigen and vimentin, negative for KL1 antigen. The clinical follow-up for about 3 years was without complications or tumor recidive. CONCLUSIONS: A differential diagnosis of a submandibular mass is the rare manifestation of a benign granular cell tumor. The neurogen origin can be proven immunohistologically by positive S-100 antigen detection. The complete surgical resection is the therapy of choice.

Biomarkers, Tumor↗

[The Roseland prosthesis].

Total joint replacement of the trapezio-metacarpal (TMC) joint is one of the procedures available for the surgical treatment of degenerative osteoarthritis or rheumatoid arthritis of the first carpometacarpal joint. A four French Alpine surgeon group, (C. Lebrun, P. Massart, F. Moutet and C. Sartorius) have developed a new cementless total TMC joint prosthesis: the Roseland prosthesis. Such a device tries to improve the biomechanical conditions of the La Caffinière's implant, which was introduced in 1973. Clinical data of a 24 patients with a 38 month mean follow-up series are reported.

Adult↗

Mutation of the IIB myosin heavy chain gene results in muscle fiber loss and compensatory hypertrophy.

The fast skeletal IIb gene is the source of most myosin heavy chain (MyHC) in adult mouse skeletal muscle. We have examined the effects of a null mutation in the IIb MyHC gene on the growth and morphology of mouse skeletal muscle. Loss in muscle mass of several head and hindlimb muscles correlated with amounts of IIb MyHC expressed in that muscle in wild types. Decreased mass was accompanied by decreases in mean fiber number, and immunological and ultrastructural studies revealed fiber pathology. However, mean cross-sectional area was increased in all fiber types, suggesting compensatory hypertrophy. Loss of muscle and body mass was not attributable to impaired chewing, and decreased food intake as a softer diet did not prevent the decrease in body mass. Thus loss of the major MyHC isoform produces fiber loss and fiber pathology reminiscent of muscle disease.

Adaptation, Physiological↗

Growth and muscle defects in mice lacking adult myosin heavy chain genes.

The three adult fast myosin heavy chains (MyHCs) constitute the vast majority of the myosin in adult skeletal musculature, and are >92% identical. We describe mice carrying null mutations in each of two predominant adult fast MyHC genes, IIb and IId/x. Both null strains exhibit growth and muscle defects, but the defects are different between the two strains and do not correlate with the abundance or distribution of each gene product. For example, despite the fact that MyHC-IIb accounts for >70% of the myosin in skeletal muscle and shows the broadest distribution of expression, the phenotypes of IIb null mutants are generally milder than in the MyHC-IId/x null strain. In addition, in a muscle which expresses both IIb and IId/x MyHC in wild-type mice, the histological defects are completely different for null expression of the two genes. Most striking is that while both null strains exhibit physiological defects in isolated muscles, the defects are distinct. Muscle from IIb null mice has significantly reduced ability to generate force while IId null mouse muscle generates normal amounts of force, but has altered kinetic properties. Many of the phenotypes demonstrated by these mice are typical in human muscle disease and should provide insight into their etiology.

Age Factors↗

Scaphoid nonunion: treatment by open reduction, bone graft, and staple fixation.

Thirty-eight scaphoid nonunions were treated by iliac crest bone grafting and staple fixation. A distractor was inserted through an anterior incision and the scaphoid was distracted to restore its original length. The nonunion was then grafted and held with a staple. Consolidation was achieved in 36 cases despite 6 cases of partial avascular necrosis. Pain at the graft site, which was usually transient, was the only complication. Wrist extension was significantly improved. The main indication for this procedure is pseudarthrosis of the middle third of the scaphoid.

Adolescent↗

Substrate specificity and stereoselectivity of horse liver alcohol dehydrogenase. Kinetic evaluation of binding and activation parameters controlling the catalytic cycles of unbranched, acyclic secondary alcohols and ketones as substrates of the native and active-site-specific Co(II)-substituted enzyme.

1. The steady-state parameters kcat and Km and the rate constants of hydride transfer for the substrates isopropanol/acetone; (S)-2-butanol, (R)-2-butanol/2-butanone; (S)-2-pentanol, (R)-2-pentanol/2-pentanone; 3-pentanol/3-pentanone; (S)-2-octanol and (R)-2-octanol have been determined for the native Zn(II)-containing horse-liver alcohol dehydrogenase (LADH) and the specific active-site-substituted Co(II)LADH. 2. A combined evaluation of steady-state kinetic data and rate constants obtained from stopped-flow measurements, allowed the determination of all rate constants of the following ordered bi-bi mechanism: E in equilibrium E.NAD in equilibrium E.NAD.R1R2 CHOH in equilibrium E.NADH.R1R2CO in equilibrium E.NADH in equilibrium E. 3. On the basis of the different substrate specificities of LADH and yeast alcohol dehydrogenase (YADH), a procedure has been developed to evaluate the enantiomeric product composition of ketone reductions. 2-Butanone and 2-pentanone reductions revealed (S)-2-butanol (86%) and (S)-2-pentanol (95%) as the major products. 4. The observed enantioselectivity implies the existence of two productive ternary complexes; E.NADH.(pro-S) 2-butanone and E.NADH.(pro-R) 2-butanone. All rate constants describing the kinetic pathways of the system (S)-2-butanol, (R)-2-butanol/2-butanone have been determined. These data have been used to estimate the expected enantiomer product composition of 2-butanone reductions using apparent kcat/Km values for the two different ternary-complex configurations of 2-butanone. Additionally, these data have been used for computer simulations of the corresponding reaction cycles. Calculated, simulated and experimental data were found to be in good agreement. Thus, the system (S)-2-butanol, (R)-2-butanol/2-butanone is the first example of a LADH-catalyzed reaction for which the stereochemical course could be described in terms of rate constants of the underlying mechanism. 5. The effects of Co(II) substitution on the different steps of the kinetic pathway have been investigated. The free energy of activation is higher for alcohol oxidation and lower for ketone reduction when catalyzed by Co(II)LADH in comparison to Zn(II)LADH. However, the free energies of binding are affected by metal substitution in such a way that the enantioselectivity of ketone reduction is not significantly changed by the substitution of Co(II) for Zn(II). 6. Evaluation of the data shows that substrate specificity and stereoselectivity result from combination of the free energies of binding and activation, with differences in binding energies as the dominating factors. In this regard, the interactions of substrate molecules with the protein moiety are dominant over the interactions with the catalytic metal ion.

Alcohol Dehydrogenase↗

Hybridization arrest of cell-free translation of the malarial dihydrofolate reductase/thymidylate synthase mRNA by anti-sense oligodeoxyribonucleotides.

In order to inhibit the in vitro translation of Plasmodium falciparum mRNA coding for the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS), oligodeoxynucleotides (ODNs) were directed against the translation initiation site or a site in the TS-coding region. In both cases considerable hybridization arrest, i.e. greater than 50% inhibition, was only achieved if the lengths of the ODNs to the two regions were 30 and 39 nucleotides, respectively, or longer. The ODN with the highest efficiency was a 49-mer directed against the TS-coding region (OTS49); 45 microM was sufficient to inhibit the expression of DHFR-TS by almost 90%. In this case the synthesis of DHFR-TS was interrupted at the binding site of OTS49 by a RNase H-independent mechanism. The resulting polypeptide was smaller (55 kDa) than one subunit of the native protein (71 kDa) and lacked TS activity.

Animals↗

The use of antisense oligonucleotides as chemotherapeutic agents for parasites.

Although several approaches to the control of human parasites are possible, the prevention and therapy of the corresponding diseases still remain a difficult task. The development of vaccines has been hampered by the poor immunological response to or the high variability of parasitic antigens. Problems also arise for chemotherapy where differences in the biochemistry of host and parasite must be exploited. The increasingly difficult search for new drugs is always challenged by the appearance of resistance.

Journal Article↗

Isolation, characterization, and chromosomal mapping of mouse P450 17 alpha-hydroxylase/C17-20 lyase.

Cytochrome P450 17 alpha-hydroxylase/C17-20 lyase (P45017 alpha) catalyzes the conversion of C-21 steroids to C-19 steroids in gonads. A full-length mouse cDNA encoding P450 17 alpha was isolated from a mouse Leydig cell library and characterized by restriction mapping and sequencing. The predicted amino acid sequence has 83% homology to rat, 66% homology to human, and 62% homology to bovine P45017 alpha amino acid sequences. The protein is 507 amino acids in length, which is 1 amino acid shorter than the human protein and 2 amino acids shorter than the bovine protein. The structural gene encoding P450 17 alpha (Cyp17) was localized utilizing an interspecific testcross to mouse chromosome 19, distal to Got-1. Another cytochrome P450, P4502c (Cyp2c), also is located at the distal end of chromosome 19. CYP17, CYP2c, and GOT1 have been mapped to human chromosome 10, with CYP2C and GOT1 mapped to the distal region, q24.3 and q25.3, respectively. The data in the present study indicate conserved syntenic loci on mouse chromosome 19 and human chromosome 10 and predict that the structural gene encoding P45017 alpha will be found distal to GOT1 on human chromosome 10.

Amino Acid Sequence↗

[Irreducible palmar dislocation of the metacarpophalangeal thumb joint by a skiing accident].

Amongst the large number of severe sprains of the lateral ulnar ligament of the metacarpophalangeal joint of the thumb by skiing accidents which we treat each year as a result of our geographical situation, we have encountered an original lesion on two occasions. The patients were referred with unstable palmar dislocation of the metacarpophalangeal joint of the thumb despite an attempt of reduction under local anaesthesia performed at the ski resort by practitioners particularly well trained in this form of traumatology. On examination, the thumb was globally painful and presented a defect of active extension of the MP joint suggestive of a complex lesion of the extensor apparatus. X-rays showed palmar dislocation of the MP joint of the thumb. Surgical exploration in both cases revealed identical lesions: complete rupture of the two bundles of the lateral ulnar ligament of the MP joint of the thumb, whose distal extremities could be seen as soon as the skin was opened with incarceration of the extensor apparatus between the palmar surface of the neck of the first metacarpal and the dorsal surface of the first phalanx. Perfectly classical treatment consisted of a dorso-lateral incision to reduce the extensor apparatus and to suture the two bundles of the lateral ulnar ligament; immediately restoring the stability which is usually observed in "classical" severe sprains. The current result is good, entirely comparable to that of severe sprains of the MP joint of the thumb.(ABSTRACT TRUNCATED AT 250 WORDS)

Follow-Up Studies↗

Quantification of changes in serotonin uptake with spinal cord injury.

The high-affinity uptake of [3H]serotonin was studied using spinal cord preparations obtained from normal dogs, dogs made paraplegic by midthoracic transection, and dogs made monoplegic by midthoracic hemisection. Measurements were made at 1, 4, and 8 weeks after surgery. Lumbar spinal cord was removed at the above time periods and a myelin-free synaptosomal fraction was obtained by centrifugation and used for studying high-affinity serotonin uptake. At 1 week, there were no significant differences for Km values (nM) among any of the three groups (138 +/- 20, 128 +/- 22, and 118 +/- 20). The Vmax values (pmol/min/mg of protein) at 1 week for the control group (4.9 +/- 0.6) versus the hemisected group (4.3 +/- 0.7) were not significantly different. The Vmax values at 1 week for the completely transected group (2.3 +/- 0.3; P less than 0.01) were significantly reduced by 53 +/- 7%. At 4 weeks, the Vmax values for the hemisected (1.8 +/- 0.2; P less than 0.05) and transected groups (0.6 +/- 0.2; P less than 0.05) were significantly different as compared to the control group. The mean percent drop in Vmax after hemisection was 56 +/- 4%, close to the predicted value of 50%. The mean percent drop in Vmax after transection was 86 +/- 2%. At 8 weeks the mean Vmax values for the hemisected (1.9 +/- 0.3; P less than 0.05) and transected (0.4 +/- 0.4; P less than 0.05) groups were not significantly different compared to their respective 4-week values. It appears that serotonin uptake can be used to quantitate roughly the degree of spinal cord injury.

Animals↗

Microvascular end-to-side arterial anastomosis using the Nd: YAG laser.

End-to-side, laser-assisted vascular anastomosis (LAVA) using a Nd: YAG laser was successfully performed on rat carotid arteries. A midline neck incision allowed isolation and approximation of both carotid arteries in an end-to-side fashion using four 10-0 nylon stay sutures. The laser parameters used for vessel fusion were 0.3-second 5-W pulses at a spot size of 600 microns. Anastomoses were analyzed at various time intervals from 1 day to 6 months by angiogram and histological examination. The anastomotic patency was 86%. Aneurysm formation occurred in 23%. Histological examination revealed an acute/subacute transmural injury both at the anastomotic site and several hundred microns away, with delayed re-endothelialization and some attempt at muscular and elastic regeneration. Histological assessment of the aneurysms demonstrated a total loss of the internal elastic lamina and muscularis. A brief discussion comparing Nd: YAG LAVA to other LAVA techniques follows.

Anastomosis, Surgical↗

Radiation-induced intracranial malignant gliomas.

The authors present seven cases of malignant gliomas that occurred after radiation therapy administered for diseases different from the subsequent glial tumor. Included among these seven are three patients who were treated with interstitial brachytherapy. Previously reported cases of radiation-induced glioma are reviewed and analyzed for common characteristics. Children receiving central nervous system irradiation appear particularly susceptible to induction of malignant gliomas by radiation. Interstitial brachytherapy may be used successfully instead of external beam radiotherapy in previously irradiated, tumor-free brain, and thus may reduce the risk of radiation necrosis.

Adult↗

The binding of 1,10-phenanthroline to specifically active-site cobalt(II)-substituted horse-liver alcohol dehydrogenase. A probe for the open-enzyme conformation.

We have studied the binding of 1,10-phenanthroline to specifically active-site cobalt(II)-substituted horse-liver alcohol dehydrogenase [Co(II)-LADH]. The dissociation constant is a factor of 6500 smaller than in the native enzyme. Spectral evidence is given which shows that 1,10-phenanthroline does not remove the catalytic Co(II) ion and that binding of 1,10-phenanthroline renders the catalytic metal ion pentacoordinate. The maximum limiting rate constant for the association of 1,10-phenanthroline to Co(II)-LADH is about 60 s-1. This is about a third of the value (169 s-1) determined for native horse-liver alcohol dehydrogenase, Zn(II)LADH [Frolich et al. (1978) Arch. Biochem. Biophys. 189, 471-480]. For cadmium(II)-substituted horse-liver alcohol dehydrogenase, [Cd(II)LADH] the maximum limiting rate constant for association of 1,10-phenanthroline increased to 590 s-1. These findings demonstrate that the rate-limiting step is strongly dependent on the chemical nature of the catalytic metal ion and its immediate environment. 1,10-Phenanthroline is shown to bind to the Co(II)-LADH.NAD+ complex in the open conformation. The maximum limiting rate constant remains unchanged in the presence of NAD+. The data have been used to derive a kinetic scheme for the formation of ternary complexes including NAD+ that involves a slow intermediary step.

Alcohol Dehydrogenase↗

Dissociation of outer-sphere water is rate-limiting for the binding of ligands in the active site of horse liver alcohol dehydrogenase.

The association of imidazole and auramine O to native horse-liver alcohol dehydrogenase [Zn(II)LADH] and active-site specifically cobalt(II)-substituted horse-liver alcohol dehydrogenase [Co(II)LADH], respectively, has been investigated. In all cases [except imidazole binding to Zn(II)LADH in the presence of auramine O] the association rates approached an upper limit (kmax). The kmax values were compared for the metal ligands imidazole (monodentate), 1,10-phenanthroline and 2,2'-bipyridine (bidentate; see also the preceding paper), and for auramine O which does not coordinate to the catalytic metal ion. Independent of the large differences in their structure and metal-bonding capability, all these compounds exhibit common, maximum, limiting rate constants of about 60 s-1 and 200 s-1 for Co(II)LADH and Zn(II)LADH, respectively. These results demonstrate that kmax is strongly dependent on the catalytic metal ion but not on the ligand. The absence of spectral changes in the d-d transitions of the catalytic Co(II) ion upon auramine O binding to Co(II)LADH indicates that the rate-limiting step is not accompanied by a major conformational change. Finally, it is concluded that reactions in the inner coordination sphere of the catalytic metal ion (i.e. the metal-bound water molecule) are not responsible for the step characterized by kmax. We propose the rate-limiting step to consist of the dissociation of one or several water molecules from the second coordination sphere of the catalytic metal ion in the active site of LADH in its open conformation.

2,2'-Dipyridyl↗

[2 cases of early "siliconitis" (silicone synovitis)].

Two cases of early silicone synovitis, 12 and 18 months after surgery for partial scaphoid implant arthroplasty (Swanson design) are reported. None of the implants had been fixed by Kirschner wire or sutured to the radius or an other carpal bone. Both implants had been immobilized for six weeks. Initially the result in both cases was good. Pain and loss of range of movement gradually increased, and a large erosive osteolytic defect of the radius was seen on the X-ray after 12 months for the first case and 18 months for the second one. Surgical revision consisted of implant removal, synovectomy with a proximal row carpectomy in the first case and a soft tissue interposition arthroplasty for the second one. The histologic examination showed a foreign body reaction with birefringent material in multinucleated giant cells. All reports about this type of silicone implant complication emphasises the role of compression forces and micro-fragmentation of the silicone. Should we continue to perform partial scaphoid implant arthroplasty from whom microparticles are creating a severe foreign body reaction?

Adult↗