Biomedical subjects

G Grosse

Publications and source records attributed to G Grosse.

At least 19 recordsLinked to original sources

PubMed2007

Differential distribution of voltage-gated potassium channels Kv 1.1-Kv1.6 in the rat retina during development.

The discharge behavior of neurons depends on a variable expression and sorting pattern of voltage-dependent potassium (Kv) channels that changes during development. The rodent retina represents a neuronal network whose main functions develop after birth. To obtain information about neuronal maturation we analyzed the expression of subunits of the Kv1 subfamily in the rat retina during postnatal development using immunocytochemistry and immunoelectron microscopy. At postnatal day 5 (P5) all the alpha-subunits of Kv1.1-Kv1.6 channels were found to be expressed in the ganglion cell layer (GCL), most of them already at P1 or P3. Their expression upregulates postnatally and the pattern and distribution change in an isoform-specific manner. Additionally Kv1 channels are found in the outer and inner plexiform layer (OPL, IPL) and in the inner nuclear layer (INL) at different postnatal stages. In adult retina the Kv 1.3 channel localizes to the inner and outer segments of cones. In contrast, Kv1.4 is highly expressed in the outer retina at P8. In adult retina Kv1.4 occurs in rod inner segments (RIS) near the connecting cilium where it colocalizes with synapse associated protein SAP 97. By using confocal laser scanning microscopy we showed a differential localization of Kv1.1-1.6 to cholinergic amacrine and rod bipolar cells of the INL of the adult retina.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Effects of brain-derived neurotrophic factor (BDNF) on glial cells and serotonergic neurones during development.

Serotonergic neurones are among the first to develop in the central nervous system. Their survival and maturation is promoted by a variety of factors, including serotonin itself, brain-derived neurotrophic factor (BDNF) and S100beta, an astrocyte-specific Ca(2+) binding protein. Here, we used BDNF-deficient mice and cell cultures of embryonic raphe neurones to determine whether or not BDNF effects on developing serotonergic raphe neurones are influenced by its action on glial cells. In BDNF-/- mice, the number of serotonin-immunoreactive neuronal somata, the amount of the serotonin transporter, the serotonin content in the striatum and the hippocampus, and the content of 5-hydroxyindoleacetic acid in all brain regions analysed were increased. By contrast, reduced immunoreactivity was found for myelin basic protein (MBP) in all brain areas including the raphe and its target region, the hippocampus. Exogenously applied BDNF increased the number of MBP-immunopositive cells in the respective culture systems. The raphe area displayed selectively reduced immunoreactivity for S100beta. Accordingly, S100beta was increased in primary cultures of pure astrocytes by exogenous BDNF. In glia-free neuronal cultures prepared from the embryonic mouse raphe, addition of BDNF supported the survival of serotonergic neurones and increased the number of axon collaterals and primary dendrites. The latter effect was inhibited by the simultaneous addition of S100beta. These results suggest that the presence of BDNF is not a requirement for the survival and maturation of serotonergic neurones in vivo. BDNF is, however, required for the local expression of S100beta and production of MBP. Therefore BDNF might indirectly influence the development of the serotonergic system by stimulating the expression of S100beta in astrocytes and the production MBP in oligodendrocytes.

Animals↗

PubMed2004

Differential effects of Rho GTPases on axonal and dendritic development in hippocampal neurones.

Formation of neurites and their differentiation into axons and dendrites requires precisely controlled changes in the cytoskeleton. While small GTPases of the Rho family appear to be involved in this regulation, it is still unclear how Rho function affects axonal and dendritic growth during development. Using hippocampal neurones at defined states of differentiation, we have dissected the function of RhoA in axonal and dendritic growth. Expression of a dominant negative RhoA variant inhibited axonal growth, whereas dendritic growth was promoted. The opposite phenotype was observed when a constitutively active RhoA variant was expressed. Inactivation of Rho by C3-catalysed ADP-ribosylation using C3 isoforms (Clostridium limosum, C3(lim) or Staphylococcus aureus, C3(stau2)), diminished axonal branching. By contrast, extracellularly applied nanomolar concentrations of C3 from C. botulinum (C3(bot)) or enzymatically dead C3(bot) significantly increased axon growth and axon branching. Taken together, axonal development requires activation of RhoA, whereas dendritic development benefits from its inactivation. However, extracellular application of enzymatically active or dead C3(bot) exclusively promotes axonal growth and branching suggesting a novel neurotrophic function of C3 that is independent from its enzymatic activity.

ADP Ribose Transferases↗

PubMed2002

Deltamethrin differentially affects neuronal subtypes in hippocampal primary culture.

The effects of deltamethrin on neuronal development and survival were studied using primary mouse hippocampal neurons in culture. Repeated applications of deltamethrin (between 2 nM and 2000 nM) decreased the number of neurons by 16-40%, respectively. Neuronal death was accompanied by an overall decrease of synaptic proteins. Deltamethrin treatment increased the K(+)-stimulated release of amino acid transmitters, GABA and glutamate. The release of the latter might also contribute to neuronal damage. A considerable number of neurons survived treatment with high concentrations of deltamethrin (200-2000 nM) and still displayed characteristics of mature neurons such as synaptic contacts or the expression of members of the Kv1 channel family. When analyzing subtypes of neurons calbindin- as well as somatostatin-positive neurons decreased by 50% after repeated treatment with 2 nM deltamethrin. Under the same conditions neuropeptide Y-positive neurons were up-regulated by 250%.Taken together these data show that deltamethrin at concentrations relevant in human toxicology differentially affects survival of neuronal subtypes by exerting either deleterious or supportive effects. We conclude that deltamethrin disturbs fine-tuning of neuronal efficiency in neuronal networks and might also interfere with the correct wiring during development.

Animals↗

PubMed2000

Expression of Kv1 potassium channels in mouse hippocampal primary cultures: development and activity-dependent regulation.

Excitability and discharge behavior of neurons depends on the highly variable expression pattern of voltage-dependent potassium (Kv) channels throughout the nervous system. To learn more about distribution, development, and activity-dependent regulation of Kv channel subunit expression in the rodent hippocampus, we studied the protein expression of members of the Kv1 subfamily in mouse hippocampus in situ and in primary cultures. In adult hippocampus, Kv1 (1-6) channel alpha-subunits were present, whereas at postnatal day 2, none of these proteins could be detected in CA1-CA3 and dentate gyrus. Kv1.1 was the first channel to be observed at postnatal day 6. The delayed postnatal expression and most of the subcellular distribution observed in hippocampal sections were mimicked by cultured hippocampal neurons in which Kv channels appeared only after 10 days in vitro. This developmental upregulation was paralleled by a dramatic increase in total K(+) current, as well as an elevated GABA release in the presence of 4-aminopyridine. Thus, the developmental profile, subcellular localization, and functionality of Kv1 channels in primary culture of hippocampus closely resembles the in situ situation. Impairing secretion by clostridial neurotoxins or blocking activity by tetrodotoxin inhibited the expression of Kv1.1, Kv1.2, and Kv1.4, whereas the other Kv1 channels still appeared. This activity-dependent depression was only observed before the initial appearance of the respective channels and lost after they had been expressed. Our data show that hippocampal neurons in culture are a convenient model to study the developmental expression and regulation of Kv1 channels. The ontogenetic regulation and the activity-dependent expression of Kv1.1, Kv1.2, and Kv1.4 indicate that neuronal activity plays a crucial role for the development of the mature Kv channel pattern in hippocampal neurons.

4-Aminopyridine↗

PubMed2000

Filiform polyposis of the colon in chronic inflammatory bowel disease (so-called giant inflammatory polyps).

On the basis of 3 of our own cases, we describe unusually intense forms of filiform polyposis and local giant polyposis as a consequence of chronic inflammatory bowel disease. The patients are: A 52-year-old woman who for 7 years has been known to have Crohn's disease (CD); a 55-year-old man who for 14 years has been known to have chronic inflammatory bowel disease, which was first thought to have been ulcerative colitis, but, as a result of the findings on the subtotal colectomy specimen, had to be classified as Crohn's disease or colitis indeterminate; and a 53-year-old woman known to have had ulcerative colitis for 37 years. From the literature on the subject, we drew up a chronological list of a total of 43 cases with similar or completely identical findings. The clinical significance of the findings in their particularly massive intensity results from their necessary differentiation--in the context of differential diagnosis--from a malignant tumor, in particular from a carcinoma in association with chronic inflammatory bowel disease, or from a villous adenoma. The indication of a need to operate results from the impossibility of being able definitely to rule out a malignant degeneration by means of clinical methods. Also, experience shows that with massive findings of the kind described a spontaneous disappearance cannot be expected. Finally, too, the clinical symptoms and the patients subjective complaints necessitate balanced surgical treatment, taking into consideration the site and the extent of the lesion.

Colectomy↗

PubMed2000

[Clinical behavior of serous and mucinous borderline tumors of the ovary with diploid DNA stem line. Follow-up studies after organ preserving and non-organ preserving therapy].

Even today, the situation is still unclear with regard to the radicality of the operation and any adjuvant therapy required in treatment of borderline tumors of the ovary. In the last two decades, treatment of these tumors in the Department of Gynecology and Obstetrics at our hospital has depended on the stage of the disease and the age of the patient. It ranged from laparoscopic cyst extirpation to hysterectomy with bilateral adnectomy and omental resection and regional lymphnodectomy. From the end of 1985 to the end of 1992, 35 patients with borderline tumors of the ovaries were operated on. Histologically, 14 borderline tumors were mucinous, 21 were serous. A follow-up investigation was carried out five to 11 years after primary operation. In this period, no patient died of borderline tumor. Twenty-eight patients who were followed up were clinically free of recurrence, five patients are alive, but could not be followed up. Two patients have died of other diseases after five years. Only one patient received adjuvant chemotherapy. She could not be followed up. In the meantime, peritoneal implants were demonstrated at second-look laparoscopies in four out of 18 patients. Later, these could no longer be demonstrated (one patient) or did not affect the survival time (three patients) and thus ultimately was not pathologically relevant. Primarily, two of these four patient had stage Ia-Ic. The paraffin blocks of the preparations are still available from 26 patients, and additional investigations could be carried out. Nineteen percent of the borderline tumors showed micropapillary structures of an MPCS (= micropapillary serous carcinoma), which evidently did not have a negative effect on the prognosis. All borderline tumors showed diploid distributions in DNA cytometry. It is not possible to make a definitive treatment recommendation on the basis of this investigation because the number of patients followed up was too small.

Adult↗

PubMed1999

SNAP-25 requirement for dendritic growth of hippocampal neurons.

Structure and dimension of the dendritic arbor are important determinants of information processing by the nerve cell, but mechanisms and molecules involved in dendritic growth are essentially unknown. We investigated early mechanisms of dendritic growth using mouse fetal hippocampal neurons in primary culture, which form processes during the first week in vitro. We detected a key component of regulated exocytosis, SNAP-25 (synaptosomal associated protein of 25 kDa), in axons and axonal terminals as well as in dendrites identified by the occurrence of the dendritic markers transferrin receptor and MAP2. Selective inactivation of SNAP-25 by botulinum neurotoxin A (BoNTA) resulted in inhibition of axonal growth and of vesicle recycling in axonal terminals. In addition, dendritic growth of hippocampal pyramidal and granule neurons was significantly inhibited by BoNTA. In contrast, cleavage of synaptobrevin by tetanus toxin had an effect on neither axonal nor dendritic growth. Our observations indicate that SNAP-25, but not synaptobrevin, is involved in constitutive axonal growth and dendrite formation by hippocampal neurons.

Animals↗

PubMed1998

Prenatal hippocampal granule cells in primary cell culture form mossy fiber boutons at pyramidal cell dendrites.

Mossy fiber boutons are the sites of synaptic signalling between hippocampal granule and pyramidal neurons. We studied the formation and localization of these terminals during development of prenatal hippocampal neurons in primary culture. Using the synaptic vesicle membrane proteins synaptophysin and synaptoporin as markers we observed that both proteins were mainly localized in perikarya and processes of fetal hippocampal neurons during the first days in vitro (DIV). Following DIV 6 synaptophysin was present in small terminals. After DIV 20 in addition large terminals immunoreactive for synaptophysin and synaptoporin were found, which were identified by electron microscopy as mossy fiber boutons impinging on pyramidal neuron dendrites. Synaptic vesicles and endosomes in the mossy fiber boutons were labeled when incubated with exogenous horseradish peroxidase, indicating that they were competent for exo-endocytosis. Taken together, our data show that hippocampal granule neurons grown in dissociated primary cultures form mossy fiber boutons containing synaptophysin and synaptoporin at pyramidal cell dendrites. Since the composition and the characteristic morphology of mossy fiber boutons formed in vitro is the same as observed in vivo we conclude that their development follows an intrinsic program.

Animals↗

PubMed1998

[Nevus cell aggregates in axillary lymph nodes in simultaneous mucinous breast carcinoma].

Nevus cell aggregates in lymph nodes are uncommon. This benign phenomenon may be difficult to differentiate from metastatic neoplasia. We report the case of a 56-year-old patient who underwent breast biopsy, followed by radical mastectomy including lymphadenectomy. Histological examination revealed solid cell aggregates as foreign tissue in the capsule of 1 of 11 identified lymph nodes devoid of any keratin immunoreaction. Strong immunohistological staining for the S-100 protein confirmed the diagnosis of nevus cell aggregates.

Adenocarcinoma, Mucinous↗

PubMed1997

[Disseminated cryptococcosis with extensive cutaneous involvement in AIDS].

BACKGROUND: Diagnosis of an ulceratively decaying indolent papule in the skin of an AIDS patient. CASE REPORT: In a 36-year-old HIV-positive man with a CD4 lymphocyte count of 60/microliters, a diagnosis of disseminated cryptococcosis was established based on a biopsy of an ulceratively decaying indolent papule in the skin of the left side gluteal region. In additional papulopustular skin lesions of neck, upper arm, upper thigh, and rima ani, Cryptococcus neoformans var. neoformans was detected by specific culture. The Cryptococcus neoformans antigen titre in serum was 1:160. The extensive cryptococcal skin involvement was accompanied by symptoms of meningeal cryptococcosis like hearing at an abnormal sound volume, a sensation of high pressure in the head and a change of behaviour, but absence of cephalgia and stiff neck. Attention is drawn to the importance of biopsy for the differential diagnosis of the skin lesions and to the significance of a specific cultural detection of Cryptococcus neoformans in view of the therapy and epidemiology of this mycosis. Under a combination therapy, consisting of amphotericin B, flucytosine and fluconazole, a healing of the skin lesions and disappearance of the neurological symptoms followed by negative cultural and serological tests were seen. Specific comments on the epidemiology of cryptococcosis in AIDS are made. CONCLUSION: In case of doubt, papulopustular skin lesions of HIV-positive patients should be biopsied. Cryptococcosis should also be considered.

AIDS-Related Opportunistic Infections↗

PubMed1997

Pathological and epidemiological aspects of skin lesions in histoplasmosis. Observations in an AIDS patient and badgers outside endemic areas of histoplasmosis.

As a consequence of HIV infection, histoplasmosis is increasingly occurring as an opportunistic infection with a systemic course outside histoplasmosis-endemic areas, e.g. in Europe. Accordingly, questions concerning the epidemiology of this mycosis arise. Two incidents involving histoplasmosis in man and badgers with prevailing involvement of the skin encouraged us to review the pathogenesis and epidemiology of this mycosis in Germany, where so far Histoplasma capsulatum has not been endemic. With a view to prevention, attention is drawn to the avoidance of microfoci of H. capsulatum in the newly introduced concept of biowaste and its composting plants in countries with modern waste management.

AIDS-Related Opportunistic Infections↗

PubMed1997

Malignant gastrointestinal lymphomas in patients with AIDS.

HIV-associated malignant lymphomas are a common complication in late HIV infection, and there is a high percentage of gastrointestinal tract involvement. Non-Hodgkin's lymphoma was found in 108 of 2,750 HIV-positive patients (3.9%) in our institution, whereas gastrointestinal manifestation was diagnosed in 48 of 108 patients (44.4%). 44 of these cases were found during endoscopy of the upper and lower gastrointestinal tract (or by laparotomy or laparoscopy in 4 cases). Endoscopy is a reliable procedure for the diagnosis of lymphoma. Unusual manifestations such as oral, esophageal or perianal lesions and multifocal disease were common findings. Life-threatening complications such as gastrointestinal bleeding, perforation, and obstruction occurred in 37.5%. High-grade B-cell lymphomas were found in all cases including mainly lymphoblastic, immunoblastic, centroblastic and Burkitt subtypes. 52% of the patients had disseminated lymphoma with Ann Arbor stage III or IV. Standard chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisone was started in 25 patients and resulted in a mean survival time of 4.8 months. The prognosis of AIDS patients presenting with malignant gastrointestinal lymphoma depends mainly on the presence or absence of previous AIDS-defining diseases, not CD4 cells, lymphoma-associated gastrointestinal complications or the histopathologic lymphoma type at the time of diagnosis.

Adult↗

PubMed1997

Fulminant primary manifestation of Crohn's colitis "Hot Crohn's disease".

Following the very short course of a disease with watery diarrhea, fever, nausea, meteorism and a severe feeling of general illness, a 22-year-old patient was diagnosed as having a toxic megacolon, and a subtotal colectomy was carried out. The postoperative progression was uncomplicated and the patient recovered quickly. The examination of the operation specimen revealed a serious ulcerous colitis with relative omission of the rectum and the distal sigmoid colon. After critical evaluation of the histological findings, it was judged to be a fulminant Crohn's colitis and, for the purposes of differential diagnosis, differentiated from ulcerative colitis and colitis indeterminate. The formal pathogenesis of the inflammatory-ulcerous processes is discussed, in particular with regard to the activation of the macrophages and the very short anamnesis in a clinically established primary manifestation of the disease.

Adult↗

PubMed1996

Cryptococcosis in HIV infection of man: an epidemiological and immunological indicator?

Cryptococcosis is an epidemiological and immunological indicator due to the absence of Cryptococcus neoformans as a saprophyte in immunocompetent humans and the advantage of specific C. neoformans culture. On this basis, a report is presented on the CD4 lymphocyte count of 36 AIDS patients suffering from cryptococcosis and other concomitant or missing opportunistic AIDS-defining infections. In 26 out of 36 patients, i.e. 72%, a CD4 lymphocyte count of < or = 50/microL (mean value 39.5%) was found. Cryptococcosis as the sole opportunistic infection was diagnosed in 5 cases (13.9%). In 31 cases, various combinations of AIDS-associated diseases were found: Pneumocystis carinii pneumonia (PCP) (n = 19), cytomegalovirus infection (CMV) (n = 10), Kaposi's sarcoma (n = 6), Mycobacterium avium intracellulare infection (MAI) (n = 5), pneumonia (n = 2), toxoplasmosis (n = 2), Candida esophagitis (n = 1), tuberculosis (n = 1), lambliasis (n = 1), salmonellosis (n = 1) and wasting syndrome (n = 5). The conspicuous simultaneous occurrence or succession of pneumocystosis and cryptococcosis and the contrasting absence of aspergillosis and mucormycosis (zygomycosis) are commented. Based on the present observations in HIV-infected persons in Berlin, a CD4 lymphocyte count of < 150/microL may be used as a parameter indicating a predisposition for cryptococcosis as an airborne AIDS-defining infection. Attention is drawn to bird droppings as the sole habitat of C. neoformans and accidental niche of various other microorganisms.

AIDS-Related Opportunistic Infections↗

PubMed1996

Brown-red pigment formation by the mycelial phase of a clinical isolate of Histoplasma capsulatum on Staib agar. A preliminary report.

In an HIV-positive patient, the suspected diagnosis of histoplasmosis capsulatum (being the first opportunistic infection indicating AIDS) on the basis of histopathological findings in biopsy material could be proved by culture on Staib agar (syn. Guizotia abyssinica creatinine agar, bird seed agar, etc.). On Staib agar, after 4 weeks at 26 degrees C, there was a cockade-like colony growth, consisting of a white centre, followed by a brown-red pigmented zone surrounded by a border of submerged mycelial growth of tan to brownish colour. Morphologically, there was a moderate formation of tuberculate macroconidia and a heavy formation of microconidia. On neutral Sabouraud's dextrose agar, there was a colony formation without pigment (albino type) free of tuberculate macroconidia and microconidia. Proposals for further investigation of these preliminary observations are made.

Adult↗

PubMed1996

[67Ga scintigraphy in retroperitoneal fibrosis (RPF): indications, application and clinical relevance--report of five patients].

AIM: The aim of the study was to evaluate the indication for 67Ga-citrate imaging and its clinical impact on patients with retroperitoneal fibrosis (RPF). METHOD: The scanning with ventral and dorsal projections was done 48 an 72 h after i.v.-injection of 370 Mbq 67Ga-citrate. RESULTS: In the 5 patients with idiopathic RPF included in the study, there was a remarkably high correlation between the clinical symptoms, the surgical and histologic findings, the activity of the disease and the results of 67Ga-scintigraphy. CONCLUSION: While CT and--maybe even better--MRI might perfectly show the extension, shape and contour of the fibrotic tissue, Gallium-67 scan appears to be superior in assessing the intensity and activity of the disease process.

Citrates↗

PubMed1995

CD4 lymphocyte count in HIV-positive persons exposed to Cryptococcus neoformans.

A report is presented on four HIV-positive homosexual men examined after several months of exposure during cleaning of a flat from masses of pigeon droppings heavily colonized by Cryptococcus neoformans. Only one out of the four persons, with a CD4 lymphocyte count of 50/microL, fell sick from systemic cryptococcosis, but not the others, with CD4 lymphocyte counts of 180, 250, and 630/microL, respectively; they remained clinically and mycologically inconspicuous and free from C. neoformans. Open questions in view of the epidemiology of opportunistic pathogens in AIDS are discussed with regard to the CD4 cell count as a parameter indicating a predisposition for cryptococcosis as an airborne AIDS-defining opportunistic infection. This has been confirmed by specific cultural diagnosis of the agent in both the environment and the patient. Already in 1987/88, the probable source of infection had been the subject of epidemiological studies on C. neoformans in Berlin.

AIDS-Related Opportunistic Infections↗