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Biomedical subjects

K H Herzog

Publications and source records attributed to K H Herzog.

At least 19 recordsLinked to original sources
PubMed1999

c-jun Is dispensable for developmental cell death and axogenesis in the retina.

Although a number of studies have implicated c-Jun in neuronal death and axonal regeneration, it is unknown whether Jun function is essential for either response. One approach to resolve this issue is to analyze knock-out mice. However, c-jun-null mice die at midgestation, precluding critical investigation. Therefore, a xenograft paradigm was used in which retinas from embryonic day 12.5 (E12.5) c-jun nullizygous or wild-type mice were transplanted onto the superior colliculus of newborn rats. The rats were allowed to develop, and the grafts were assayed at various times for cell death and axon growth. Histologically, grafts of both genotypes developed in identical manners and had morphological characteristics of retinas. A functional c-jun allele was not essential for axogenesis, because ganglion cells in retinal grafts from c-jun nullizygous mice developed axons that projected into the colliculus. Programmed cell death (PCD) was also evident in the age-appropriate regions of the retina in both wild-type and c-jun-null grafts. Furthermore, there were no discernible differences in the number or location of dying cells in the two genotypes. That c-jun was not essential for PCD was supported by two additional findings. First, a c-jun-lacZ reporter gene was expressed in many cells in developing and grafted retinas, although only a few of these cells were destined to die. Second, in E12.5 c-jun-null embryos there were normal levels of PCD in the trigeminal ganglion. Together, these data indicate that c-Jun is not essential for axon growth in the retina or for PCD in the retina and trigeminal ganglion.

Alleles↗
PubMed1999

Neuroprotection by a caspase inhibitor in acute bacterial meningitis.

Half of the survivors of bacterial meningitis experience motor deficits, seizures, hearing loss or cognitive impairment, despite adequate bacterial killing by antibiotics. We demonstrate that the broad-spectrum caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone (z-VAD-fmk) prevented hippocampal neuronal cell death and white blood cell influx into the cerebrospinal fluid compartment in experimental pneumococcal meningitis. Hippocampal neuronal death was due to apoptosis derived from the inflammatory response in the cerebrospinal fluid. Apoptosis was induced in vitro in human neurons by inflamed cerebrospinal fluid and was blocked by z-VAD-fmk. As apoptosis drives neuronal loss in pneumococcal meningitis, caspase inhibitors might provide a new therapeutic option directed specifically at reducing brain damage.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Requirement for Atm in ionizing radiation-induced cell death in the developing central nervous system.

Ataxia telangiectasia (AT) is characterized by progressive neurodegeneration that results from mutation of the ATM gene. However, neither the normal function of ATM in the nervous system nor the biological basis of the degeneration in AT is known. Resistance to apoptosis in the developing central nervous system (CNS) of Atm-/- mice was observed after ionizing radiation. This lack of death occurred in diverse regions of the CNS, including the cerebellum, which is markedly affected in AT. In wild-type, but not Atm-/- mice, up-regulation of p53 coincided with cell death, suggesting that Atm-dependent apoptosis in the CNS is mediated by p53. Further, p53 null mice showed a similar lack of radiation-induced cell death in the developing nervous system. Atm may function at a developmental survival checkpoint that serves to eliminate neurons with excessive DNA damage.

Animals↗
PubMed1998

Contributions of the optic tectum and the retina as sources of brain-derived neurotrophic factor for retinal ganglion cells in the chick embryo.

Retinal ganglion cells (RGC) are supported by brain-derived neurotrophic factor (BDNF), but it is not known if BDNF acts as a target-derived factor or as an afferent or autocrine trophic factor. Here we demonstrate that BDNF mRNA is expressed in the retinorecipient layer of the chick optic tectum as well as in the inner nuclear layer and ganglion cell layer of the retina. Amacrine cells rather than RGC were the main source of BDNF mRNA in the ganglion cell layer, as determined by in situ hybridization that was combined with retrograde labeling of RGC and destruction of RGC by optic stalk transection, followed by quantitative RT-PCR. Cells in the ganglion cell layer as well as the retinorecipient layers of the optic tectum were BDNF-immunolabeled. After injections into the tectum, radio-iodinated BDNF was transported to the retina where autoradiographic label accumulated in the inner plexiform and ganglion cell layers. After intraocular injection, iodinated BDNF accumulated in these same retinal layers and correlated with the distribution of p75 neurotrophin receptor protein. The majority of cross-linked receptor-bound BDNF in the retina immunoprecipitated with p75 antibodies. No difference in the intensity of BDNF immunolabel was observed in the experimental retina or tectum after optic stalk transection, indicating that most of the BDNF in the RGC was not derived from the optic tectum. These data indicate that a substantial fraction of the BDNF in the ganglion cell layer is derived from local sources, afferents within the retina, rather than from the optic tectum via retrograde transport.

Animals↗
PubMed1997

The Ca2+ binding protein, frequenin is a nervous system-specific protein in mouse preferentially localized in neurites.

Frequenin is a Ca2+-binding protein that has been implicated in the regulation of neurotransmitter release at the neuromuscular junction [15,16]. However, its cellular and subcellular localization in brain have not been determined. Therefore, we cloned mouse frequenin (Mfreq) and investigated its expression both in vivo and in vitro. The amino acid sequence of Mfreq is homologous to that of frequenins from other species. Northern and Western blot analyses indicated that the Mfreq mRNA is a single species of 4.2 kb, and that the protein has a mass of 24 kDa protein on SDS gel, respectively. Expression of Mfreq is nervous system specific. However, Mfreq mRNA and protein are widely distributed in the brain, spinal cord, and dorsal root ganglia. Mfreq is expressed in early embryonic brain and the levels of Mfreq remain high throughout development. In situ hybridization and immunocytochemistry demonstrated that Mfreq is expressed primarily in neurons and presumptive astrocytes. The Mfreq protein was preferentially localized in neurites (dendrites and axons). Double immunofluorescence microscopy established that Mfreq was co-localized with the dendritic marker, MAP-2 and the synapse marker, SV2 in cultured hippocampal neurons. The distribution and subcellular localization of Mfreq may help understand its cellular function.

Amino Acid Sequence↗
PubMed1997

Expression of INK4 inhibitors of cyclin D-dependent kinases during mouse brain development.

In situ hybridization of mouse embryo sections demonstrated expression of mRNAs encoding two polypeptide inhibitors (p18INK4c and p19INK4d) of cyclin D-dependent kinase (CDK) 4 and CDK6 in the central nervous system. No expression of two other INK4 members, p16INK4a and p15INK4b, was observed. The p19INK4d and p18INK4c proteins formed complexes with either CDK4 or CDK6 in a temporal pattern consistent with the results of in situ hybridization. Expression of INK4c was observed at embryonic day 13.5 in neuroepithelial zones of the developing brain, being restricted to dividing neuroblasts but absent from differentiating postmitotic neurons. In the neocortex, p18INK4c was expressed precisely at those developmental stages when neuroblasts switch from a symmetric to an asymmetric pattern of cell division with concomitant increases in their G1 interval. INK4d RNA was detected from embryonic day 11.5 onward, at higher levels than INK4c and with a distinctly different spatial and temporal pattern. Marked INK4d expression was seen in dorsal root ganglia, spinal cord, and focally throughout the brain, but primarily in postmitotic neurons. Neural expression of INK4d continued postnatally into adulthood in postmitotic cells of the dentate gyrus, the pyramidal layer of the hippocampus, and in discrete regions of the cerebral cortex, cerebellum, thalamus, and brainstem. Downregulation of p19INK4d in the dentate gyrus after kainic acid-induced seizures indicated that its expression could also be modified in nondividing cells by excitotoxic stress. Therefore, p19INK4d may contribute to maintaining the quiescent state, acting as a buffer to prevent reactivation of cyclin D-dependent kinases in terminally differentiated cells.

Animals↗
PubMed1995

[Ultrasound differential diagnostic aspects in cystadenoma of the pancreas].

AIM: Assessment of differential diagnostic criteria of cystic adenomas of the pancreas. METHOD: We rechecked on all diagnostic criteria of patients with pancreatic pseudocysts retrospectively who had been treated in our department between 1981 and 1993. RESULTS: 12 patients with cystic adenomas of the pancreas had been treated in our department i.a. 7.8% of all cystic pancreatic tumours. Histopathologically 1 microcystic and 4 macrocystic adenomas as well as 7 cystic adenocarcinomas were seen. CONCLUSION: Diagnostic ultrasound criteria are discussed. Ultrasound-guided fine--needle-biopsy (FNB) is necessary to diagnose the content as well as the status of the pancreatic cysts. The ultrasound and the fine-needle-biopsy findings are important for differentiating between cystic adenomas and pseudocysts of the pancreas.

Adenocarcinoma↗
PubMed1995

[Esophagus carcinoid--a rare differential diagnosis in malignant esophageal neoplasia].

Two of patients with a carcinoid tumor of the esophagus are reported, an extremely rare localisation. Eight months after esophagectomy the 50-year-old male is entirely well and without any sign of recurrence; the 56-year-old female has died in this time. Our two cases are discussed in comparison with seven cases found in the literature.

Carcinoid Tumor↗
PubMed1994

Expression of the BDNF gene in the developing visual system of the chick.

Using a sensitive and quantitative method, the mRNA levels of brain-derived neurotrophic factor (BDNF) were determined during the development of the chick visual system. Low copy numbers were detected, and BDNF was found to be expressed in the optic tectum already 2 days before the arrival of the first retinal ganglion cell axons, suggesting an early role of BDNF in tectal development. After the beginning of tectal innervation, BDNF mRNA levels markedly increased, and optic stalk transection at day 4 (which prevents subsequent tectal innervation) was found to reduce the contralateral tectal levels of BDNF mRNA. Comparable reductions were obtained after injection of tetrodotoxin into one eye, indicating that, already during the earliest stages of target encounter in the CNS, the degree of BDNF gene expression is influenced by activity-dependent mechanisms. BDNF mRNA was also detected in the retina itself and at levels comparable to those found in the tectum. Together with previous findings indicating that BDNF prevents the death of cultured chick retinal ganglion cells, these results support the idea that the tightly controlled expression of the BDNF gene might be important in the co-ordinated development of the visual system.

Animals↗
PubMed1990

Excessive urinary oxalate excretion after combined renal and hepatic transplantation for correction of hyperoxaluria type 1.

A 4.5-year-old boy received a combined liver and kidney transplant for correction of hyperoxaluria type 1. Both organs were from the same donor and functioned primarily. Three months after transplantation, urine oxalate excretion reached a maximum of 10,500 mumol/24 h and remained above 2300 mumol/24 h for the next 2 months. Two months later, oxalate excretion decreased to about 565 mumol/24 h, indicating exhaustion of a large oxalate pool. Six months after transplantation plasma oxalate is near normal (4.9 mumol/l). With the exception of one episode of acute rejection of the renal transplant, both organs were tolerated well and continue to have a unimpaired function 9 months after transplantation. However, there is increased echogenity on renal ultrasound, indicating oxalate deposits in the grafted kidney. This case illustrates that successful combined transplantation of both liver and kidney can be performed in infants, resulting in cure of the metabolic defect. The prolonged or acute excretion of oxalate may lead to oxalate deposition in the grafted kidney without impaired graft function or early graft loss.

Child, Preschool↗
PubMed1990

Neurothelin: an inducible cell surface glycoprotein of blood-brain barrier-specific endothelial cells and distinct neurons.

The blood-brain barrier is characterized by still poorly understood barrier and transport functions performed by specialized endothelial cells. Hybridoma technology has been used to identify a protein termed neurothelin that is specific for these endothelial cells. Neurothelin is defined by the species-specific mouse mAb 1W5 raised against lentil-lectin-binding proteins of neural tissue from embryonic chick. In the posthatch chick, neurothelin expression is found on endothelial cells within the brain but not on those of the systemic vascular system. Injection of the monoclonal antibody in vivo leads to labeling of brain capillaries, indicating that the corresponding antigen is expressed on the luminal surface of brain endothelial cells. Transplantation of embryonic mouse brain onto the chick chorioallantoic membrane results in rodent brain vascularization by the avian vascular system. Subsequently, normally mAb 1W5-negative endothelial cells, originating from blood vessels of the chick chorioallantoic membrane, are induced to express neurothelin when they are in contact with mouse neural tissue. In contrast to differentiated brain neurons that do not express neurothelin, neurons of the nonvascularized chick retina synthesize neurothelin. However, neurothelin is not found on retinal ganglion cell axons terminating on 1W5-negative brain cells. 1W5 immunoreactivity was also found in the pigment epithelium that forms the blood-eye barrier. Putting epithelial cells into culture results in concentration of neurothelin at cell-cell contact sites, leaving other cell surface areas devoid of antigen. Therefore, the distribution of neurothelin appears to be regulated by cell-cell interactions. In Western blot analysis, neurothelin was identified as a protein with a molecular mass of approximately 43 kD. The protein bears at least one intramolecular disulfide bridge and sulfated glucuronic acid as well as alpha-D-substituted mannose/glucose moieties. The exclusive neurothelin expression in the posthatch chick on endothelial cells of the central nervous system but not on systemic endothelial cells makes neurothelin a marker specific for blood-brain barrier-forming endothelial cells. The spatiotemporally regulated neurothelin expression in neurons suggests an interaction between vascularization and neuronal differentiation.

Allantoin↗
PubMed1990

Particulate (high-molecular-mass) and soluble alkaline phosphatase in urine determined by high-performance liquid chromatography.

We detected in urine by HPLC two enzyme fractions of alkaline phosphatase (AP, EC 3.1.3.1), soluble and particulate, analogous to those in serum. The second fraction was eluted with high-salt-content eluent at the same elution time as high-molecular-mass, or particulate, AP in serum. AP characterization in urine from a patient with acute rejection crisis showed a greater sensitivity of the particulate form to treatment with L-phenylalanine, which suggests a higher content of intestinal-type AP in the particulate form. The soluble fraction showed a more liver-type AP behavior. Changes in the chromatograms after the sample was treated with 1-butanol and Triton X-100 support a membrane origin of the particulate AP. Urinalyses from patients with acute renal disease showed increased activity of soluble and particulate AP, with a relatively greater increase of particulate AP.

Adult↗
PubMed1989

[Surgical treatment of hemorrhaging gastroduodenal ulcer. Individually adapted indications].

Increase in application of emergency gastroscopy together with indications according to "Forrest" criteria, in the course of nine years, resulted in reduction of lethality by 15 per cent among patients who had been surgically treated for bleeding ulcers. Life-threatening postoperative risks were higher without gastroscopy. A critical appraisal is made in this paper of gastroscopic findings, with reference being made to surgical results.

Aged↗
PubMed1989

High-molecular-mass ("biliary") isoenzyme of alkaline phosphatase and the diagnosis of liver dysfunction in cystic fibrosis.

The high-Mr isoenzyme of alkaline phosphatase (AP, EC 3.1.3.1), a highly sensitive index to cholestasis, was measured by liquid chromatography in 45 patients with cystic fibrosis. Results of serum tests for liver dysfunction--including gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, total AP, bilirubin, and bile acids--were compared with those for high-Mr AP. Values for high-Mr AP were increased in 44.4% of our patient population, with activities ranging from 0.4 to 17.3 U/L. The upper limit in the control group was 2.5 U/L. We find increased high-Mr AP to be a more sensitive indicator of liver dysfunction in patients with cystic fibrosis than are other tests.

Adolescent↗
PubMed1988

Transient hyperphosphatasaemia of infancy.

In five patients with benign transient hyperphosphatasaemia (THP), high activities of so-called "atypical" alkaline phosphatase or fragment isoenzymes were detected. One case occurred after rotavirus infection. Incubation with neuraminidase suggested that "atypical" alkaline phosphatase originated from highly glycosylated bone and liver isoenzymes. This may have been due to virus-induced low isoenzyme clearance from serum. The course of isoenzyme activities in THP following rotavirus infection was followed. Determination of atypical alkaline phosphatase may be useful in the diagnosis of THP.

Alkaline Phosphatase↗