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R Lange

Publications and source records attributed to R Lange.

At least 163 records · Page 9Linked to original sources

TnTIN and TnTAP: mini-transposons for site-specific proteolysis in vivo.

Tobacco etch virus (TEV) protease recognizes a 7-aa consensus sequence, Glu-Xaa-Xaa-Tyr-Xaa-Gln-Ser, where Xaa can be almost any amino acyl residue. Cleavage occurs between the conserved Gln and Ser residues. Because of its distinct specificity, TEV protease can be expressed in the cytoplasm without interfering with viability. Polypeptides that are not natural substrates of TEV protease are proteolyzed if they carry the appropriate cleavage site. Thus, this protease can be used to study target proteins in their natural environment in vivo, as well as in vitro. We describe two TnS-based mini-transposons that insert TEV protease cleavage sites at random into target proteins. TnTIN introduces TEV cleavage sites into cytoplasmic proteins. TnTAP facilitates the same operation for proteins localized to the bacterial cell envelope. By using two different target proteins, SecA and TolC, we show that such modified proteins can be cleaved in vivo and in vitro by TEV protease. Possible applications of the site-specific proteolysis approach are topological studies of soluble as well as of inner and outer membrane proteins, protein inactivation, insertion mutagenesis experiments, and protein tagging.

Adenosine Triphosphatases↗

A stable partly denatured state of trypsin induced by high hydrostatic pressure.

The effect of hydrostatic pressure on the unfolding of trypsin was studied by fluorescence spectroscopy under pressure from 1 to 7000 bar. It was found that, at pH 3.0 or pH 7.3, a stable partly denatured state of trypsin was obtained when the applied pressure was about 6.5 kbar. This transient denatured state did not show any enzymatic activity and was different from that denatured by 8 M urea or high temperature in both intrinsic fluorescence spectrum and 8-anilino-1-naphtalene sulfonate (ANS) binding, having some obvious characteristics of 2 molten globule state of protein. It was also found that the formation of this partly denatured state of trypsin was temperature dependent. Energenic values of the process were also given.

Anilino Naphthalenesulfonates↗

The effect of high pressure on thermolysin.

The effects of high pressure on thermolysin activity and spectroscopic properties were studied. Thermolysin showed distinct pressure-induced activation with a maximum observed at 200-250 MPa for a dipeptide amide substrate and at 100-120 MPa for a heptapeptide substrate. By examining the pressure dependence of the hydrolytic rate for the former substrate using a high pressure stopped-flow apparatus as a mixing device under elevated pressures, the activation volume of the reaction was -71 ml mol(-1) at 25 degrees C. Delta V++ was accompanied by a negative activation expansibility and a value of -95 ml mol(-1) was obtained at 45 degrees C. A prolonged incubation of thermolysin under high pressure, however, caused a time-dependent deactivation. These changes due to pressure were monitored by several spectroscopic methods. The fourth-derivative absorbance spectrum showed an irreversible change, mostly in the tyrosine and tryptophan regions, at a pressure higher than 300 MPa. Intrinsic fluorescence and circular dichroism measurements of thermolysin in solution also detected irreversible changes. All these measurements indicated that a change occurred at higher pressures and are explained by a simple two-state transition model accompanied by a large, negative change in the volume of reaction.

Biochemistry↗

Heterotopic auxiliary liver transplantation in a 3-year-old boy with acute liver failure and aplastic anemia.

BACKGROUND: Auxiliary liver transplantation offers an alternative method to conventional transplantation in acute liver failure. It is especially challenging for children because lifelong immunosuppression may be avoided. However, experience with this procedure is rare and there is controversy about whether to place the graft orthotopically or heterotopically. METHODS: We present the case of a 3-year-old boy with acute liver failure due to non-ABC hepatitis complicated by aplastic anemia who underwent auxiliary liver transplantation. Segments 2 and 3 of the graft were implanted heterotopically in the right lower abdomen. RESULTS: Good liver function was immediately restored. Aplastic anemia resolved 3 weeks after transplantation. Immunosuppressive therapy was discontinued after 14 months, and the graft was left to atrophy. Thirty-nine months after transplantation the boy is alive and well with normal liver function tests and normal blood cell counts. CONCLUSIONS: Heterotopic auxiliary liver transplantation allowed recovery of the native liver in a child with acute liver failure and aplastic anemia due to non-ABC hepatitis.

Abdomen↗

Dynamics of carbon monoxide binding with cytochromes P-450.

The dynamics of CO rebinding with cytochromes P-450cam, P-450scc, and P-450LM2 after laser flash photolysis have been investigated from 293 to 77 K, and the distribution functions of the rate parameters P(k) and of the activation enthalpy P(H) were determined using the maximum entropy method. In a fluid solvent, geminate rebinding is nonexponential, presumably because of a spectral shift induced by protein relaxation on the same time scale. Substrate binding increases the yield of the bimolecular process and decreases the bimolecular rate by 1 or 2 orders of magnitude. The amplitude of these effects seems to correlate with substrate specificity. In a rigid environment at low temperature, cytochromes P-450 exhibit a bimodal distribution of activation enthalpy; P(H) consists of two distinct bands which are in a thermal equilibrium even at 77 K. The results lead to a scheme in which a common structural perturbation splits the conformational substates of cytochromes P-450 into pairs of "doublet" substates with different dynamic properties. The hierarchy of conformational substates of cytochromes P-450 thus contrasts with that of oxygen-binding hemoproteins such as myoglobin.

Adrenal Cortex↗

The role of phenylalanine 31 in maintaining the conformational stability of ribonuclease P2 from Sulfolobus solfataricus under extreme conditions of temperature and pressure.

Ribonuclease P2 from the thermophilic archaebacterium Sulfolobus solfataricus is a small protein (7 kDa) with a known three-dimensional structure. Inspection of the structure and molecular dynamics simulation reveal that three aromatic residues (Phe5, Phe31, and Tyr33) from the hydrophobic core have a strong van der Waals interaction energy. We studied the thermodynamics of the heat, cold, and pressure-induced protein conformational changes of the wild type and of the F31A and F31Y mutants by analyzing the protein UV absorbance in the fourth derivative mode. The wild-type protein was extremely stable under all conditions of temperature and pressure. Heat and cold denaturation of both mutants, as well as denaturation by pressure of the F31A mutant, led to significant blue shifts of the derivative spectrum, indicating increased solvent exposure of Tyr33. For the F31Y mutant, high pressure (400 MPa) protected the protein against thermal denaturation. This study, probing the properties of the hydrophobic aromatic core, complements a thermal unfolding study which probes the overall structural changes [Knapp, S., Karshikoff, A., Berndt, K. D., Christova, P., Atanasov, B., & Ladenstein, R. (1996) J. Mol. Biol. 264,1132-1144]. The differences observed in response to extremes of temperature, pressure, and pH may be rationalized by an unfolding mechanism involving larger parts of the peripheral protein while the integrity of the hydrophobic core is maintained.

Enzyme Stability↗

Value of an extended monoethylglycinexylidide formation test and other dynamic liver function tests in liver transplant donors.

Measuring monoethylglycinexylidide (MEGX) formation after intravenous administration of lidocaine in potential organ donors (MEGX test) has been advocated as a useful test to select donor livers for transplantation, but some groups have demonstrated a low test efficacy. We, therefore, investigated the value of an extended MEGX formation test and the value of other dynamic liver function tests, in selecting suitable human donor livers. In 51 human multi-organ donors, we measured elimination of galactose, indocyanine green, and lidocaine, as well as formation of MEGX, at 15, 30, and 60 min after administration of the test substances. In the early postoperative period, the function of the transplanted liver was then classified as good or poor, as defined by a prothrombin time above or below 65% by day 4 and fibrinogen concentration above or below 300 mg/dl by day 7. Donor characteristics and preservation modalities were very similar between the two groups. Galactose, indocyanine green, and lidocaine metabolism failed to predict good or poor graft function in the early postoperative period. MEGX serum concentrations, however, were significantly higher in the group of donors whose organs functioned well in the recipients, as compared with donors whose organs functioned poorly in the recipients. This was true for MEGX concentrations at 15 min (117+/-9 vs. 90+/-9 ng/ml; P=0.03), 30 min (108+/-8 vs. 86+/-8 ng/ml; P=0.04), and 60 min (100+/-6 vs. 73+/-5 ng/ml; P=0.006). Extending the MEGX formation test from 15 to 60 min improved test efficacy. Maximal MEGX concentration in 9 or up to 12 consecutive blood samples, drawn between 3 and 120 min after lidocaine infusion, was also significantly higher in donors whose organs functioned well, than in donors whose organs functioned poorly (129+/-10 vs. 101+/-10 ng/ml; P=0.03). Although the groups with good and poor organ function differed significantly with respect to their MEGX serum concentrations, and although efficacy of the MEGX test was improved by extending the test from 15 to 60 min, the overlap in individual MEGX serum concentrations was still so wide that it is virtually impossible to predict early graft function only on the basis of the MEGX test in the donor. Therefore, the MEGX test, although of potential scientific interest, does not predict early graft function with an accuracy necessary for clinical use.

Adult↗

Preservation of pig liver allografts after warm ischemia: normothermic perfusion versus cold storage.

Warm ischemia is known to induce substantial damage to the liver parenchyma. With respect to clinical liver transplantation, the tolerance of the liver to warm ischemia and the preservation of these organs have not been studied in detail. In isolated reperfused pig livers we proceeded according to the following concept: Livers were subjected to 1 or 3 h of warm ischemia. Subsequently, these organs were preserved by either normothermic perfusion or cold storage (histidine-tryptophan-alpha-ketoglutarate, HTK) for 3 h each. After storage, liver function was assessed in a reperfusion circuit for another 3 h. Parameters under evaluation were bile flow, perfusion flow, oxygen consumption, enzyme release into the perfusate (creatine kinase, glutamic oxaloacetic transaminase (GOT), lactic dehydrogenase, and glutamic pyruvic transaminase), and histomorphology. Damage to the liver was lowest after warm ischemia of 1 h. The results after cold storage were superior to those after normothermic perfusion (GOT: 3.2 +/- 0.3 and 2.6 +/- 0.2 U/g liver; cumulative bile production: 14.7 +/- 2.1 and 9.4 +/- 1 ml, respectively; P < 0.05). In contrast, we found substantial damage at the end of reperfusion in livers undergoing 3 h of warm ischemia under both preservation techniques with severe hepatocellular pyknoses and essentially altered nonparenchymal cells. The results suggest that pig livers undergoing 1 h of warm ischemia and cold storage for 3 h with HTK solution may lead to functioning after transplantation.

Alanine Transaminase↗

[Dynamic cardiomyoplasty].

Between 1965 and 1995 the incidence of heart failure has been constantly rising and the mortality from this disease has increased fivefold. The introduction of ACE-inhibitors and of adrenergic beta-blockers have resulted in major symptomatic improvements in patients with mild to moderate heart failure. For end-stage disease, heart transplantation offers by now the only therapeutic option and yields excellent results. The permanent implantation of left heart assist-devices is just gaining increasing importance. Yet, both methods also have inherent drawbacks and may not be available to all patients, so that new methods are constantly evaluated. Cardiomyoplasty was introduced into clinical practice in 1985 by Alain Carpentier and since then more than 700 patients have been operated worldwide. After dissection of the latissimus dorsi muscle it is wrapped around the heart in a clockwise fashion (Figure 1). Two sensing electrodes are placed on the anterior aspect of the right ventricle and two stimulation electrodes between the proximal branches of the thoracodorsal nerve (Medtronic SP 5548). The electrodes are then connected with a burststimulator (Cardiomyostimulator, Medtronic 4710) (Figure 2). During the first 2 weeks following the operation the muscle is not stimulated in order to allow for the healing process. Thereafter, a stimulation protocol with a programmed, staged increase of the stimulation frequency is started, to induce transformation of the skeletal muscle into a "fatigue resistant" tissue. After 3 months the muscle is stimulated with every second heart beat (2:1 mode) with full burstimpulses containing 6 single impulses per burst for a duration of 185 ms (Figure 3). Cardiomyoplasty was conceived for patients in NYHA III and severely impaired myocardial function, in whom drug treatment does not produce the expected benefits. The criteria for patient selection are strictly followed, since it has been shown in the past, that the preoperative condition of the patient is of specific importance for the postoperative outcome. Contraindications are NYHA IV, advanced right ventricular dysfunction, secondary pulmonary hypertension (> 600 dyn x s x cm-5), LV end-diastolic diameter > 70 mm und AV-valve incompetence > Grad II. Between July 1985 und October 1996 647 patients received a cardiomyoplasty with the Medtronic Cardiomyoplasty System and the results from 438 patients were analyzed from the "Worldwide Cardiomyoplasty Study Group". One and 2 years following the operation NYHA-class had improved by one class in 41.9% and 53.3%, respectively, and by 2 classes in 38.1% and 30.5%, respectively. In 16% and 15% no improvement was found (Figure 4). Prospective investigation of the quality of life by a score revealed a considerable improvement in the level of daily activities and social interaction. In contrast, two years after the operation, only a small, but significant increase in LV-EF from 22.9 +/- 8.1% to 25.8 +/- 9.7% (p < 0.05) was shown. Heart rate, maximal O2-consumption, total exercise time, cardiac index, stroke volume and stroke work index did not change. According to the results of a recent FDA-study, in-hospital mortality was 12% between 1991 and 1993, and was reduced during a second phase starting 1994 to < 3%. One, 2 and 3-year survival of 349 patients who were in NYHA-III prior to the operation was 69%, 56% und 47%, respectively. 43 patients who were operated in NYHA IV exhibited considerably worse survival with only 48% after 1 year and 30% after 2 years, respectively. In a subgroup of 103 patients with a statistically low operative risk, 1, 2 and 3-year survival was 77%, 71% und 61%, respectively (Figure 5). As a mechanism of action the skeletal muscle wrap exerts some active improvement of systolic wall motion of the heart/skeletal muscle complex. However, probably more important is an acute and chronically persisting shift of the pressure-volume relation to the left. This process results in a "reverse remodel

Cardiomyoplasty↗

Hemofiltration increases IL-6 clearance in early systemic inflammatory response syndrome but does not alter IL-6 and TNF alpha plasma concentrations.

OBJECTIVE: To test the hypothesis that continuous hemofiltration increases interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) clearances and results in decreased cytokine plasma concentrations independent of renal function in patients with early SIRS. DESIGN: Prospective, controlled, randomized study. SETTING: Intensive care units at a university hospital. PATIENTS: 28 consecutive patients who fulfilled the criteria of the systemic inflammatory response syndrome (SIRS). INTERVENTIONS: Patients with SIRS were randomly assigned to either a hemofiltration or a control group irrespective of renal function. In patients of the hemofiltration group an isovolemic hemofiltration was initiated directly after the diagnosis of SIRS and maintained for at least 48 h. MEASUREMENTS AND RESULTS: A significant (p < 0.001) increase in total IL-6 clearance (hemofiltrate + urine), but not in TNF alpha clearance, was observed with hemofiltration. However, the plasma concentrations of both cytokines remained unchanged. Hemodynamic variables did not change significantly. CONCLUSIONS: Continuous hemofiltration increases IL-6 plasma clearance but not TNF alpha clearance. However, hemofiltration failed to decrease plasma concentrations of TNF alpha and IL-6 and, therefore, cannot be used effectively for cytokine elimination in SIRS. Accordingly, beneficial effects occasionally reported with hemofiltration are unlikely to be expected due to elimination of IL-6 or TNF alpha.

Adult↗

Conventional and quantitative liver function tests after hepatic transplantation: a prospective long-term follow-up.

In long-term survivors of liver transplantation, hepatic function is obviously of vital importance. Therefore, we prospectively performed conventional and quantitative liver function tests in patients who had survived a first transplantation for at least 4 years. Compared to 6 months after transplantation, serum bilirubin concentration and gamma GT activity were significantly lower after 3, 4, and 5 years (bilirubin 1.2 +/- 0.2 mg/dl at 6 months vs 1.0 +/- 0.1, 1.0 +/- 0.2, and 0.8 +/- 0.1 mg/dl respectively; gamma GT 106 +/- 0 33 U/l at 6 months vs 56 +/- 17, 67 +/- 35, 39 +/- 10 U/l respectively). At these points in time, blood levels of cyclosporin A were also significantly lower. Other parameters of liver cell function and liver cell integrity (AP, AST, ALT, GLDH, total protein, thromboplastin time, partial thromboplastin time) were unchanged over time. Serial quantitative liver function tests (indocyanine green half-life, galactose elimination capacity, lidocaine half-life, and MEGX formation) also remained stable. Thus, we conclude that hepatic function remains stable in long-term survivors of liver transplantation for at least several years.

Adult↗

Successful regrafting of a transplanted liver.

We report on the successful regrafting of a transplanted liver. The donor liver was first grafted into a patient suffering from cryptogenic cirrhosis; the patient died 1 day after the elective transplantation of cerebral bleeding. The well-functioning graft was harvested again and transferred to our institution. After another 12 h of cold ischemia, the liver was reperfused in an urgently registered patient with recurrence of hepatitis B in his first graft. The transplantation was successfully performed and the patient is now doing well, more than 5 months after regrafting with the reused liver.

Humans↗

[Animal experiment studies of arterialization of the portal vein in liver transplantation using the Göttingen minipig].

The aim of the present experimental investigation was to assess the circulatory, biochemical and histopathological consequences of complete portal vein arterialization of the transplanted liver in 'Göttinger' miniature pigs. Orthotopic liver transplantations using a passive portojugular shunt were performed in six male 'Göttinger' miniature pigs. Using an iliac artery segment interposition of the animal donor, the hepatic artery (HA) of the transplant liver was anastomized end-to-end and the portal vein (PA) also united with the internal iliac artery stump end-to-end. The central anastomosis was performed onto the suprarenal aorta. Portal vein blood was drained into the infrahepatic caval vein via an end-to-side shunt (PCS). During the course, the following parameters were determined: arterial blood pressure, venous pressure, cardiac output, electromagnetic blood flow measurements across the HA, PA, and PCS, PA mean pressure, transaminases, partial thromboplastin time and fibrinogen. Liver biopsies and autopsy specimens were investigated. One of six animals died a few hours postoperatively, two of six died after 48 and 72 h, respectively, whereas three pigs survived the scheduled 7 days. The cardiac output fell intraoperatively initially by an average of 20% but had approximately the starting volume of 2.2 l/min at the end of the operation. Although the diameter of the anastomosis was reduced to 4 mm, the flow in the arterialized PA on average was 340 ml/min when the vessel clamp was opened. At the end of operation the mean was 380 ml/min, the interval of measurement being 75 min. The flow across the PCS and the HA were constant during the course. As mechanism for this phenomenon, autoregulation of the liver blood flow on a sinusidal level has been suggested. The biochemical results and the histopathological findings showed no change compared to previous findings in a control group of animals in which liver transplantation was performed by our team. Complete arterialization of the PA is well tolerated in liver transplantation in 'Göttinger' miniature pigs with regard to circulation and liver function in a short-term trial of a maximum of 7 days. Long-term results are still to come.

Anastomosis, Surgical↗

Protection from acetaminophen-induced liver damage by the synergistic action of low doses of the poly(ADP-ribose) polymerase-inhibitor nicotinamide and the antioxidant N-acetylcysteine or the amino acid L-methionine.

1. An array of therapeutically used analgetic and antirheumatic drugs cause severe liver damage. The present study investigates the hepatoprotective effects of inhibitors of NAD-dependent adenoribosylation reactions and of antioxidants in analgesic-induced hepatic injury. 2. Male NMRI mice were treated PO with 500 mg/kg of acetaminophen, and the activities of both glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) were determined in serum. 3. The acetaminophen-induced release of both GOT and GPT from injured liver cells could be inhibited in a dose-dependent manner, when mice were injected additionally either with increasing amounts (from (25 mg/kg to 100 mg/kg i.p.) of the PARP-inhibitor nicotinamide, with increasing amounts (from 25 mg/kg to 100 mg/kg i.p.) of the antioxidant N-acetylcysteine, or with increasing amounts (from 50 mg/kg to 300 mg/kg i.p.) of the amino acid L-methionine. 4. A combination of both nicotinamide and N-acetylcysteine (at the low dose of 12.5 mg/kg i.p. each) results in a complete protection from acetaminophen-induced release of GOT and GPT from injured liver cells. 5. A combination of both L-methionine and N-acetylcysteine or nicotinamide (at the low dose of 12.5 mg/kg IP each) resulted also in complete protection from acetaminophen-induced release of GOT and GPT.

Acetaminophen↗

Spinal cord protection using hypothermic cardiocirculatory arrest in extended repair of recoarctation and persistent hypoplastic aortic arch.

OBJECTIVE: In recurrent coarctation collateral circulation may not be sufficient to maintain adequate perfusion of the lower body during the period of surgical repair. Different techniques such as interposition of a Gott-shunt, use of left heart bypass or hypothermic cardiocirculatory arrest are used to prevent spinal cord injury. METHODS: Twenty-eight operations for recurrent coarctation were performed in 26 patients following end-to-end anastomosis (58%), patch plasty (21%), subclavian flap aortoplasty (14%) and graft interposition (7%). Associated cardiac defects were present in 77% of the patients. Eleven patients who had adequate (> 50 mmHg) distal perfusion pressure during a test occlusion were operated on using simple cross-clamping (group I, mean age 8.5 +/- 3.8 years). In group I, end-to-end anastomosis was performed in nine patients and graft interposition in two patients. In 17 cases (including two patients from group I) with insufficient collateral circulation and with persistent hypoplasia of the arch, hypothermic cardiocirculatory arrest was used (group II, mean age 12.8 +/- 9.6 years). In group II end-to-end anastomosis was performed in three patients and graft interposition in 14 patients. Mean bypass-time was 116 +/- 36 min and arrest-time 33 +/- 16 min. Hypothermic cardiocirculatory arrest was begun when nasopharyngeal temperature was below 20 degrees C, corresponding to a rectal temperature of 24 +/- 3 degrees C. RESULTS: Hypothermic cardiocirculatory arrest allowed open reconstruction of the arch and/or complete or partial replacement of the arch and the coarctation segment. In-hospital mortality was 0 and 5.9% in group I and II, respectively. The one patient who died in group II had simultaneous correction of an anomalous pulmonary venous connection and death was unrelated to the method of coarctation repair. Reversible laryngeal nerve paresis was observed in two patients in group II, no other neurologic complications were observed in either group. Postoperative gradients over the repair site were less than 20 mmHg by Doppler-echocardiography. Two patients of group I had to have a second, early reoperation because of stenosis at the anastomotic site. Reconstruction of the distal aortic arch was then performed during hypothermic cardiocirculatory arrest. CONCLUSIONS: The use of hypothermic cardiocirculatory arrest in this special indication is a safe method which allows open reconstruction of the coarctation site and the aortic arch and protection of the spinal cord. The need for early reoperation because of inadequate repair may be reduced.

Anastomosis, Surgical↗

Effect of buffering on pharmacokinetics of ketoprofen enantiomers in man.

AIMS: Concomitant administration of magnesium hydroxide may affect the rate or extent of absorption of non-steroidal anti-inflammatory drugs. In order to find out whether or not buffering modifies the pharmacokinetics of ketoprofen, plasma concentration-time courses resulting from oral administration of unbuffered formulations were compared with those of buffered formulations. METHODS: Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25 mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p. l.c. up to 24 h post-dose. RESULTS: Maximum plasma concentrations (Cmax) of both the (R)- and (S)-enantiomer, observed after administration of the buffered formulations (12.5 and 25 mg), were higher compared with the unbuffered tablets by about 50-80%. The area under concentration-time data (AUC) was unaffected, and, hence, Cmax/AUC was increased by buffering. Time to Cmax (tmax) and mean residence time (MRT) tended to be or was shortened by buffering. CONCLUSIONS: It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected.

Adult↗

Analyses of meiotic chromosomes in testicular biopsies of infertile patients.

Between 1989 and 1992 meiotic chromosome studies and synaptonemal complex analyses were evaluated using light and, in part, electron microscopy in 46 infertile males with highly abnormal spermiograms. This examination focused on whether the breakdown of spermatogenesis could be attributed to pairing anomalies of bivalents. The study of meiotic chromosomes and synaptonemal complexes indicated normal spermatogenesis in five patients (11%); in the remainder, maturation arrest was diagnosed. In 21 individuals (50%) the breakdown was accompanied by pairing anomalies (asynapsis, fragmented synaptonemal complexes, X/Y univalence). Thus it is shown that male infertility can often partly be explained by meiotic disorders.

Atrophy↗