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Biomedical subjects

R Schmitt

Publications and source records attributed to R Schmitt.

At least 19 recordsLinked to original sources

Maintenance DNA methyltransferase (Met1) and silencing of CpG-methylated foreign DNA in Volvox carteri.

DNA methylation plays an important role in the gene-silencing network of higher eukaryotes. We have analyzed the 21.5-kb maintenance methyltransferase (M-MTase) gene, met1, of the multicellular green alga Volvox carteri. The met1 transcript was detected only during the period when DNA replication and cell division are taking place. It encodes a 238 kDa protein containing eight C-terminal activity domains typical of M-MTases, plus upstream DNA-binding domains including the ProDom domain PD003757, which experimental analyses in animal systems have indicated is required for targeting the enzyme to DNA-replication foci. Several insertions of unknown function make Volvox Met1 the largest known member of the Met1/Dnmt1 family. Here we also show that several endogenous transposon families are CpG-methylated in Volvox, which we think causes them to be inactive. This view is supported by the observation that an in vitro CpG-methylated gene introduced into Volvox was maintained in the methylated and silent state over >100 generations. Thus, we believe that Met1 recognizes and perpetuates the in vitro methylation signal, and that the silencing machinery is then able to transduce such a methylation-only signal into a stable heterochromatic (and silent) state.

Algal Proteins↗

Carpal instability.

This review addresses the pathoanatomical basics as well as the clinical and radiological presentation of instability patterns of the wrist. Carpal instability mostly follows an injury; however, other diseases, like CPPD arthropathy, can be associated. Instability occurs either if the carpus is unable to sustain physiologic loads ("dyskinetics") or suffers from abnormal motion of its bones during movement ("dyskinematics"). In the classification of carpal instability, dissociative subcategories (located within proximal carpal row) are differentiated from non-dissociative subcategories (present between the carpal rows) and combined patterns. It is essential to note that the unstable wrist initially does not cause relevant signs in standard radiograms, therefore being "occult" for the radiologic assessment. This paper emphasizes the high utility of kinematographic studies, contrast-enhanced magnetic resonance imaging (MRI) and MR arthrography for detecting these predynamic and dynamic instability stages. Later in the natural history of carpal instability, static malalignment of the wrist and osteoarthritis will develop, both being associated with significant morbidity and disability. To prevent individual and socio-economic implications, the hand surgeon or orthopedist, as well as the radiologist, is challenged for early and precise diagnosis.

Biomechanical Phenomena↗

[Functional anatomy and biomechanics of the carpus].

The wrist is an exceedingly complex structure composed of several joints and a dedicated ligamentous system. Its functional principles allow a wide range of carpal motion and make the wrist remarkably resistant to external stress forces:The proximal carpal row serves as an intercalated link interposed between the static elements of both the forearm and the distal carpal row. Like a flexible place-holder, the proximal row synchronously adapts to the spatial and temporal requirements of the wrist. There are synergistic movement patterns including simultaneous flexion of the proximal row as the wrist is deviated radially and simultaneous extension during ulnar deviation. Together with pronosupination of the radioulnar joints, the combined radial/ulnar inclination and flexion/extension enable spherical, out-of-plane movements of the hand. Carpal function is best explained by the "model of a ring under tension."This review addresses the anatomy and the biomechanics of the wrist and illustrates systematic image analysis by using carpal lines and angles as well as indices of carpal height.

Biomechanical Phenomena↗

[Scaphoid fracture and nonunion: current status of radiological diagnostics].

Scaphoid fractures, which involve approximately two-thirds of all wrist injuries, are often not detected during initial radiographic examination. By using high-resolution CT and dedicated MRI, it is possible to recognize scaphoid fractures soon at the first diagnostic approach and to assess fragment stability. CT imaging provides all the relevant information of the fracture extent and of the fracture healing in the follow-up. MRI is most sensitive in the detection of scaphoid fractures; however, fracture signs must be differentiated from those of a bone bruise. Both the initially overseen scaphoid fracture and the unsuccessful healing can lead to the natural history of scaphoid nonunion. In the injured scaphoid, CT imaging is essential for depicting the osseous morphology, whereas contrast-enhanced MRI is crucial for assessing the viability of the proximal fragment.

Fractures, Bone↗

[Early radiological diagnostics for scapholunate dissociation (SLD)].

The partial tear of the scapholunate ligament (pre-dynamic stage of SLD) as well as the complete tear (dynamic stage) does not lead to carpal malalignment. However, if the completely ruptured ligament is accompanied by lesions of the extrinsic ligaments, both the scaphoid and the lunate are malaligned already at rest (static stage of SLD). Later, osteoarthritis will develop, beginning in the radioscaphoid compartment, progressing to the midcarpal joint, and ending in a carpal collapse (osteoarthrotic stage of SLD). Dynamic SLD is detectable only in stress views and in cinematography. The high utility of MRI for directly visualizing the injured ligament is emphasized: reparation tissue is focally enhanced at the rupture site by intravenously applied contrast agent; the individual segments of the scapholunate ligament can be visualized in direct MR arthrography, therefore allowing differentiation of partial and complete ligamentous tears.

Humans↗

Expression of hypoxia-inducible transcription factors in developing human and rat kidneys.

Early kidney development is associated with the coordinated branching of the renal tubular and vascular system and hypoxia has been proposed to be a major regulatory factor in this process. Under low oxygen levels, the hypoxia-inducible transcription factor (HIF) regulates the expression of genes involved in angiogenesis, erythropoiesis and glycolysis. To investigate the role of HIF in kidney development, we analyzed the temporal and spatial expression of the oxygen regulated HIF-1alpha and -2alpha subunits at different stages of rat and human kidney development. Using double-staining procedures, localization of the HIF target geneproducts vascular endothelial growth factor (VEGF) and endoglin was studied in relation to HIFalpha. In both species, we found marked nuclear expression of HIF-1alpha in medullary and cortical collecting ducts and in glomerular cells. In contrast, HIF-2alpha was expressed in interstitial and peritubular cells podocytes of the more mature glomeruli. After completion of glomerulogenesis and nephrogenesis, HIF-1alpha and -2alpha were no longer detectable. The HIF-target gene VEGF colocalized with HIF-1alpha protein in glomeruli and medullary collecting ducts. HIF-2alpha colocalized with the endothelium-associated angiogenic factor, endoglin. Both HIFalpha isoforms are activated in the developing kidney in a cell-specific and temporally controlled manner, indicating a regulatory role of oxygen tension in nephrogenesis. HIF-1alpha seems to be primarily involved in tubulogenesis and HIF-2alpha in renal vasculogenesis. Both isoforms are found in glomerulogenesis, potentially having synergistic effects.

Animals↗

European attempts to set guidelines for improving diagnostics of autoimmune rheumatic disorders.

The rational way to set a diagnosis and estimate a prognosis in rheumatology is to start by setting a tentative diagnosis and then follow a fixed scheme for laboratory testing, eg, by using an agreed algorithm. The use of order algorithms can be extended to post-test algorithms that will assist clinicians in approaching the right diagnosis and prognosis. New methods used in autoimmune serology do not deliver results that can be directly compared to those of older methods, and thus the new methods need to be thoroughly tested with sera from differential diagnostically relevant disease controls to set a clinically meaningful cut-off for positivity. Borderline positive results need to be treated with special care to avoid misuse. Early diagnosis is of great importance, and serological results can be very useful if used the right way. European efforts to secure rational diagnostic work-up in autoimmune rheumatic disease have led to a better dialogue between clinicians and laboratory scientists in several countries.

Algorithms↗

Comprehensive MR angiography of the lower limbs: a hybrid dual-bolus approach including the pedal arteries.

The purpose of this study was to include the pedal vasculature into the coverage of peripheral multistation magnetic resonance angiography (3DceMRA). A total of 216 patients suffering from peripheral vascular disease were examined with a modified hybrid dual-bolus technique. The cruropedal arteries were acquired first with two sagittal slabs and time-resolved 3D sequences. Then the aortofemoral vessels were visualized using the bolus-chase technique and a second contrast injection. Interventional procedures were performed in 104 patients, and in 69 of those, the cruropedal vessels were also examined with digital subtraction angiography (iaDSA). Using 3DceMRA, the cruropedal arteries were displayed with both excellent and good quality in 95% (205/216 cases), and without any venous overlay in 94% (203/216 cases). The aortofemoral vessels were not jeopardized by the first contrast injection. With iaDSA as the standard of reference, observed sensitivity of 3DceMRA was found in ranges from 80% (29%, 99%) to 100% (86%, 100%) for assessing significant stenoses, and observed specificity ranged between 93% [80%, 98%] and 100% (82%, 100%). In conclusion, hybrid dual-bolus 3DceMRA significantly reduces the limitations of standard single-bolus 3DceMRA in anatomic coverage and temporal resolution of the cruropedal arteries, thus providing high-quality images of the entire peripheral vasculature.

Aged↗

[Force distribution in the wrist following scaphotrapeziotrapezoid arthrodesis].

Scaphotrapeziotrapezoid (STT) arthrodesis has been proposed to stabilise the radial column and to redirect the load away from the lunate. Midterm effects on force transmission are still unclear. Six patients who were treated with triscaphe arthrodesis were examined after an average of 5 years using CT osteoabsorptiometry of both wrists. STT arthrodesis had been performed in four cases with Kienböck's disease type IIIb and in two cases of scaphotrapeziotrapezoid arthritis. At all contralateral wrists peak mineralisations were found beyond the lunate fossa and in the scaphoid fossa of the distal radius. At the side with STT arthrodesis there was only one peak. In five cases this density maximum was beyond the scaphoid fossa and in one case half beyond the lunate and half beyond the scaphoid fossa. Triscaphe arthrodesis allows load transmission from the lunate to the radial column.

Arthritis↗

[Differential diagnosis of the signal-compromised lunate in MRI].

PURPOSE: To define both the underlying pathology and diagnostic criteria in lunates presenting with conspicuous signal pattern in MRI. MATERIALS AND METHODS: The retrospective evaluation of 2940 MRI examinations revealed 203 patients with signal alterations of the lunate. All MRI examinations were performed on 1.5-Tesla platforms using dedicated surface coils and an intravenous contrast agent. To establish a definitive diagnosis, a total of 252 MRI examinations (49 follow-ups), 22 CT examinations and 4 arthroscopic studies were obtained in addition to the obligatory conventional radiographs. RESULTS: Incorporating all clinical data, radiographs and MRI examinations succeeded in assigning a diagnosis in 136 signal-compromised lunates (67.0 %), whereas additional diagnostic procedures or follow-up examinations were required for the definitive diagnosis in 57 cases (33.0 %). The most frequent entities were 51 cases of Kienbock's disease (25.1 %), 47 cases of ulnolunate-(triquetral) impaction syndromes (23.2 %) and 44 cases of intra-osseous ganglion cysts (21.7 %). Other pathologies included 23 degenerative, 19 traumatic and 10 inflammatory changes as well as 9 congenital conditions. For MRI assessment of the altered lunate, the most important parameters were location and morphology as well as involvement of the articular and osseous structures of the carpus. CONCLUSION: The lunate may be affected by different pathological states of the wrist. In total, only one quarter of the signal-compromised lunate represented Kienboeck's disease.

Adolescent↗

[Wrist lesions in MRI arthrography compared with wrist arthroscopy].

BACKGROUND: Wrist arthroscopy is routinely used for diagnosis of ligamentous lesions to the wrist. Although it is very sensitive and specific, it is also more invasive than other available diagnostic techniques. METHOD: In a prospective trial, 125 patients (80 men, 45 women) 37 years old (+/- 12) with clinical evidence of wrist lesions were evaluated with direct wrist arthro MRI. Within 24 hours following direct arthro MRI wrist arthroscopy was performed. The surgeons and radiologists were not aware of the other results until completion of their investigation. Specificity, sensitivity, positive predictive value, negative predictive value and accuracy were determined. RESULTS: According to the MRI findings, lesions of the TFCC were suggested in 70 patients (56 % of all patients). In 65 cases this was confirmed by wrist arthroscopy. In the remaining 55 patients no TFCC lesions were detected by MRI. However in three cases TFCC lesions were found by arthroscopy. In the remaining 52 patients MRI accurately excluded TFCC lesions. There was a correlation of MRI and arthroscopy in detecting TFCC lesions in 93.6 %. Sensitivity was 94 %, specificity 89 %, positive predictive value 91 % and negative predictive value 93 %. Complete scapholunate ligament tears were detected by MRI in 12 (9.6 %) cases. Correlation with wrist arthroscopy was 99 %, sensitivity 92 %, specificity 100 %, positive and negative predictive value 100 % and 99 %, respectively. Accuracy for incomplete scapholunate lesions (n = 17, 13.6 %) and lunotriquetral tears (n = 4, 3.2 %) was poor (sensitivity 59 % and 25 %, specificity 100 % and 99 %). CONCLUSION: Though sensitivity of MRI arthrography approaches that of arthroscopy, it cannot replace it at the moment. However, it is a potent additional tool for wrist diagnosis if intraarticular contrast is used. It can facilitate diagnosis and indications for surgery of the wrist. It may make arthroscopic and more invasive interventions for diagnostic purposes avoidable in future.

Adult↗

[Scaphoid fractures--operative or conservative treatment? A CT-based classification].

Traditionally acute scaphoid fractures were treated by immobilization. As a consequence we have to deal with a high number of scaphoid non-unions or SNAC wrists. A study of 30 patients with scaphoid non-union showed that only 30% (9 patients) have not seen a doctor, while the majority of the patients (70%, 21 patients) were treated by a physician after trauma. In 15 (71.4%) of these 21 patients a missed diagnosis and in 6 (28.6%) a failed conservative treatment of the scaphoid fracture were the reasons for scaphoid non-union. Therefore, improvements in the diagnosis and therapy of scaphoid fractures are urgently needed. Herbert's classification of scaphoid fractures provides the underlying rationale for treatment according to the fracture type seen on X-ray. Differentiation between stable and unstable fractures sometimes is difficult from conventional X-rays. In these cases we recommend a CT bone scan in the long axis of the scaphoid. According to the CT scan we modified Herbert's classification: undisplaced waist fractures are classified as stable and can be treated conservatively or can be stabilized percutaneously using minimally invasive procedures. Comminuted or displaced fractures are classified as unstable and need operative treatment because of the increased risk of scaphoid non-union after plaster immobilization. Fractures of the proximal pole of the scaphoid should be treated operatively by internal fixation, even if they are not displaced, because of the reduced perfusion. We recommend a CT scan of the scaphoid, if there is any doubt about the diagnosis or the stability of the scaphoid fracture. In any case, a CT scan has to be ordered to justify a conservative treatment.

Adolescent↗

[Osteoid osteoma of the hand and wrist].

PURPOSE: Osteoid osteoma is a painful benign bone tumour and very rare in the hand and wrist. Diagnosis may be very difficult and often is made after multiple previous diagnostic errors. METHODS AND PATIENTS: From 1992 until 2003, 22 patients (11 men, 11 women) were operated on because of an osteoid osteoma of the hand or wrist in our hospital. The mean age was 30 years, ranging from 14 to 62 years. We retrospectively analysed patient records. A clinical examination with X-ray control was performed in 14 patients. Five patients were questioned by phone; three patients were lost to follow-up. RESULTS: The mean time interval between onset of symptoms and surgical removal of the tumour was approximately two years. Symptoms were often non-specific; clinical findings varied according to localisation of the tumour. Conventional X-rays did not always show typical pathological findings. Bone scanning and gadolinium-enhanced MRI proved to be very sensitive in detecting the pathological process. High-resolution CT-scan demonstrated the nidus exactly. Usually, operative removal of the nidus resulted in immediate pain relief. At follow-up, 18 patients were free of pain. However seven patients had had a revision operation; in four of those, osteoid osteoma recurred once again. CONCLUSIONS: In our opinion, it is important to consider osteoid osteoma as a possible cause of otherwise unexplained pain of the hand or wrist. If there is clinical suspicion, we recommend the early use of gadolinium-enhanced MRI as a sensitive screening method. Thus, it should be possible to shorten the time interval until correct diagnosis is established.

Adolescent↗

[Diagnostic angiography using multi-slice spiral CT in acute obstruction of the basilar artery].

OBJECTIVE: To evaluate the diagnostic efficiency of CT angiography in case of clinical signs of acute brainstem infarction for the therapeutic management of catheter-based local thrombolysis. MATERIAL AND METHODS: 3 patients (2 males, 1 female) suffering from an acute onset of brainstem symptoms and being suspicious of an occluded basilar artery were included into this report. 1 patient underwent selective vertebral arteriography. 2 patients were initially examined with CT angiography using a 4-row scanner and 100 ml intravenous contrast agent. RESULTS: In one patient, an occlusion of the basilar artery was excluded with catheter-based angiography. Subsequently, the patient was treated with systemic thrombolysis using r-tPA because of a thalamus infarction seen in MRI. 2 patients who have been initially examined with CT angiography presented with complete occlusions of the basilar arteries. These patients underwent r-tPA thrombolysis by means of superselective micro-catheter approaches of the vertebrobasilar vessels. CT angiography was very useful for determinating the occlusion length of the basilar artery pre-therapeutically, and in 1 case for ruling out an occluded vertrebral artery for catheterization. All patients recovered well under thrombolytic therapy applied systemically or selectively. CONCLUSION: Cerebral multi-slice CT angiography is a fast and save technique for detecting or ruling out an acute basilar artery occlusion. Thus, in cases of equivocal clinical signs CT angiography is recommended before the decision of thrombolytic therapy is made.

Adult↗

Antidepressants for generalized anxiety disorder.

BACKGROUND: Pharmacological treatments have been successfully used to treat Generalized Anxiety Disorder (GAD). The mainstay for the pharmacological treatment of GAD in past decades has been the use of benzodiazepine and non benzodiazepine anxiolytics. Data emerging over the last two decades have shown that antidepressants may be equally effective to anxiolytics for treating GAD. The use of antidepressants for treating GAD may be advantageous, due to the fact that GAD presents a high co morbidity ratio with major depressive disorder (62%) and dysthymia (37%). OBJECTIVES: To assess the efficacy and acceptability of antidepressants for treating generalized anxiety disorder. SEARCH STRATEGY: Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register - CCDANCTR (up to May 2002), Anxiety Neurosis (up to May 2002) and Cochrane Controlled Trials Register (CENTRAL/CCTR) (up to May 2002), MEDLINE (1966 to May 2002), LILACS (1982 to May 2002); reference searching; personal communication; conference abstracts and book chapters on the treatment of generalized anxiety disorder. SELECTION CRITERIA: Randomised controlled trials were included. Exclusion criteria were: non randomised studies; studies which included patients with generalized anxiety disorder and another Axis I co-morbidity. DATA COLLECTION AND ANALYSIS: The data from studies were extracted independently by two reviewers and relative risks, weighted mean difference and number needed to treat were estimated. People who died or dropped out were regarded as having had no improvement. MAIN RESULTS: Antidepressants (imipramine, venlafaxine and paroxetine) were found to be superior to placebo in treating GAD. The calculated NNT for antidepressants in GAD is 5.15. Dropout rates did not differ between antidepressants. Only one study presented data on imipramine and trazodone. Imipramine was chosen as the reference drug and, therefore, data on trazodone could not be included in the meta analysis. Only one study was conducted among children and adolescents (Rynn 2001). The latter study showed very promising results of sertraline in children and adolescents with GAD, which warrants its replication in larger samples. REVIEWER'S CONCLUSIONS: The available evidence suggests that antidepressants are superior to placebo in treating GAD. There is evidence from one trial suggesting that paroxetine and imipramine have a similar efficacy and tolerability. There is also evidence from placebo-controlled trials suggesting that these drugs are well tolerated by GAD patients. Further trials of antidepressants for GAD will help to demonstrate which antidepressants should be used for which patients.

Antidepressive Agents↗

[TFCC-lesion. MR arthrography vs. arthroscopy of the wrist].

In a blinded study from January to July 2000, 125 patients suffering from specific complaints of the wrist were examined with direct MR arthrography prospectively. Within 24 hours an arthroscopy of the wrist was performed. With the MR arthrography in 70 patients or 56% of all patients injury of the TFCC was diagnosed. In 65 patients this could be verified arthroscopically. In the remaining 55 patients no TFCC lesion was diagnosed with the MR arthrography. However lesions were found via arthroscopy in three cases,were MRI findings expected an intact TFCC. In the remaining 52 cases the MRT could exclude a lesion of the TFCC correctly. An agreement of the MRT and arthroscopic results could be determined in 93.6% of the cases (correlation). The diagnosis of a TFCC lesion by means of MRI was correct in 94% of the cases (sensitivity), the exclusion of such lesion in 89% (specificity). Positive or negative predictive values of 91% or 93% were achieved. Since neither a specificity nor a sensitivity of 100% can be reached at the moment, the MR arthrography cannot replace the arthroscopy. However it could be a potent additional tool for wrist diagnosis if intraarticular contrast is used. It can facilitate the diagnostics and the indication for surgery at the ulnocarpal wrist and help to reduce arthroscopic interventions that are only for diagnostic purposes and without any therapeutic consequences. With improvement of the technique of magnet resonance tomography we can expect further increase of accuracy and the clinical use of the MR arthrography in the diagnostic workup at the ulnocarpal wrist.

Adult↗

[Direct MR arthrography of the wrist in comparison with arthroscopy: a prospective study on 125 patients].

OBJECTIVE: In literature the diagnostic value of MRI for detecting lesions of the carpal ligaments and the TFCC is judged controversially. The aim of the following study is to determine the diagnostic accuracy of direct MR arthrography for depicting and staging of intraarticular lesions of the wrist. MATERIAL AND METHODS: One day before undergoing arthroscopy, 125 patients suffering from wrist pain were examined with direct MR arthrography in a prospective and blinded study. A mixture of contrast medium (iodine-containing contrast medium and gadopentetate in relation 200 : 1) was injected into both radiocarpal and midcarpal joints. The following sequences were acquired on a 1.5T scanner: coronal T1-weighted SE, coronal fat-saturated T1-weighted SE, coronal T1-/T2*-DESS-3D, and sagittal T2*-weighted MEDIC. MRI results were compared with arthroscopic findings using statistical analysis (SEN = sensitivity, SPE = specificity, PPV = positive predictive value, NPV = negative predictive value, ACC = accuracy). RESULTS: In comparison to arthroscopy as the accepted diagnostic gold standard, the following results were found for MR arthrography. Detection of TFCC lesions: SEN 97.1 %, SPE 96.4 %, PPV 97.1 %, NPV 96.4 %, ACC 96.8 %. Detection of complete tears of the scapholunate ligament: SEN 91.7 %, SPE 100 %, PPV 100 %, NPV 99.1%, ACC 99.2%. Detection of partial tears: SEN 62.5 %, SPE 100 %, PPV 100 %, NPV 94.8 %, ACC 95.2 %. Detection of cartilage defects: SEN 84.2 %, SPE 96.2 %, PPV 80 %, NPV 97.1 %, ACC 94.4 %. In total, only three lesions of the lunotriquetral ligament were present. CONCLUSION: Direct MR arthrographic imaging is well suited for detecting intraarticular lesions of the wrist. The presented diagnostic results of MR arthrography are superior to the results of unenhanced MRI reported in the literature. Direct MR arthrography as a reliable diagnostic tool is strongly recommended if lesions of the scapholunate ligament and the triangular fibrocartilage complex are suspected. In contrast, an attitude of caution must be adopted in diagnosing lesions of the articular cartilage of the wrist.

Adolescent↗

Identification of differentially expressed genes in models of melanoma progression by cDNA array analysis: SPARC, MIF and a novel cathepsin protease characterize aggressive phenotypes.

Currently, the scale and consistency of changes of gene expression profiles in models of melanoma progression are largely unknown. Therefore, we investigated siblings of cell lines or malignant melanomas (MM), which have been selected by nude mouse passages for (a). increased tumorigenicity (local ECM-independent growth), (b). metastatic potential, or (c). selected for increase invasiveness using the Boyden chamber. cDNA array analysis surveying more than 27.000 transcripts per cell line showed that 1.5-2.8% of all detectable transcripts were consistently differentially regulated during selection process in those models. Using array analysis, we identified 33 individual transcripts that exhibited significant differential hybridization paralleling the increased aggressiveness of the selected progeny. Because some of those genes could play a significant functional role in the progression of MM, we additionally proved their regulative pattern using Northern blotting. Among others, progressive overexpression of osteonectin/SPARC, a angiogenesis, was found in the selected offspring from all three experimental models and may therefore be considered as a potential marker for aggressive MM as well a promising therapeutic target. We further show that the selection of MM cells for increased ECM-independent local growth was accompanied by overexpresssion of macrophage migration inhibiting factor (MIF), an important modulator of both cell cycle progression and angiogenesis, and cathepsin Z, a novel member of the family of matrix degrading proteinases.

Animals↗