Costimulation improves the killing capability of T cells redirected to tumor cells expressing low levels of CD33: description of a novel modular targeting system.

Owing to their clinical success, there is growing interest in novel bispecific antibodies (bsAbs) for retargeting of T cells to tumor cells including for the treatment of acute myeloid leukemia (AML). One potential target for retargeting of T cells to AML blasts is the surface molecule CD33. Here we describe a novel modular targeting platform that consists of a universal effector module (EM) and individual target modules (TMs). Both modules can form an immune complex via a peptide epitope. The resulting targeting complex can functionally replace a conventional bsAb. By fusion of a costimulatory domain (for example, the extracellular CD137 ligand domain) to the TM, the targeting complex can even provide a costimulatory signal to the redirected T cells at their side of interaction with the tumor cell. Furthermore, we observed that an efficient killing of tumor cells expressing low levels of the tumor target CD33 becomes critical at low effector-to-target cell ratios but can be improved by costimulation via CD137 using our novel targeting system.

Strategy of treatment of submucosal gastric tumors.

BACKGROUND: The more frequent use of endoscopic ultrasonography (EUS) leads to an increased number of diagnosed gastric submucosal tumors (G-SMT). Since until now rather little therapeutical success in respect of these tumors has been achieved, we evaluated our concept of watchful waiting and selective treatment of patients with G-SMT in an analysis of prospectively collected data. PATIENTS AND METHODS: Forty-seven consecutive patients with G-SMT treated at our institution between 1994 and 2000, were included. All patients underwent abdominal ultrasound and EUS, and in case of suspicious findings or a tumor size > 2 cm EUS fine needle aspiration (EUS-FNA) was performed. Patients were operated on if a malignant tumor was suspected (tumor size > 2 cm; detection of metastases) or if complications occurred (e.g. bleeding, ulceration). RESULTS: All 47 patients were included in this study. Typical symptoms were nausea (64%), bleeding (11%) and pain (9%). EUS showed a G-SMT averaging 6.4 (0.8 - 30) cm in size. EUS-FNA was performed in 24 patients revealing PAP III (n = 1), PAP II (n = 21) and PAP I (n = 2) scores. Surgery was performed in 33 patients, revealing gastrointestinal stromal tumors (GISTs) in 18 patients as well as several other malignant and non-malignant lesions. During follow-up (median 37 months), none of the conservatively treated patients (n = 14) developed a malignant tumor. CONCLUSIONS: In one third of our patients surgery could be avoided with this strategy. No delayed diagnosis of a malignant tumor during follow-up was established. Small G-GMT's should be monitored conservatively if diagnostic procedures and follow-up was performed by EUS and eventually EUS-FNA.

Heterotopic pancreas--clinical presentation and pathology with review of the literature.

BACKGROUND/AIMS: Heterotopic pancreas is usually a silent gastrointestinal malformation, but it may become clinically evident when complicated by chronic inflammation or by growth. METHODOLOGY: We report on eleven cases of heterotopic pancreatic tissue. The cases were selected from the records of our Surgical Department and Institute of Pathology. The literature about heterotopic pancreas is reviewed. RESULTS: Nausea and vomiting (27%), epigastric pain (27%), ulceration (27%) and weight loss (18%) were the three most frequent symptoms and signs. The lesions were diagnosed as gastrointestinal tumor or ulcer by gastroduodenoscopy (36%). The other patients were diagnosed during surgery (64%). Definitive diagnosis was only achievable by pathology. Heterotopic pancreas was the reason for surgery in 36% of the cases, in another 45% diagnosis was incidental during surgery and in 18% the diagnosis was established endoscopically and surgery was not necessary. CONCLUSIONS: The diagnosis of heterotopic pancreas is rarely established, most cases remain clinically silent. In symptomatic patients diagnosis should to be secured histologically to exclude malignant disease.

Multiple vascular abnormalities and a paradoxical combination of vitamin B12 deficiency and thrombocytosis in a case with POEMS syndrome.

POEMS/Crow-Fukase syndrome is a rare multisystem disorder associated with elevated vascular endothelial growth factor (VEGF), which clinically presents with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. We report a case of POEMS syndrome due to a gammopathy of undetermined significance with thrombocytosis, vitamin B(12) deficiency, highly elevated VEGF and in addition to glomeruloid angiomas two previously undescribed proliferative vascular lesions: a spinal arteriovenous fistula and a plexogenic pulmonary arteriopathy, which ultimately resulted in lethal pulmonary hypertension. We assume that the high VEGF levels caused the vascular abnormalities observed in our patient.

[Cysticercosis as a rare cause of a tumor of the tongue]. / Zystizerkose als seltene Ursache einer Raumforderung der Zunge.

This article presents the case of a 19-year-old male patient with cysticercosis in the tongue and the CNS. It also presents images of histological sections of the cysticercus parasite situated in the tongue muscles and CT and MRI images of cerebral clusters. Cysticercosis is a disease caused by the hydatid of the porcine tapeworm (cysticercus). Cysticercus normally dwells in the organs of pigs. Infection of human tissues is much more unusual and affliction of the oral cavity can be regarded as a rarity. In this case the patient complained about a painless, clearly delineated induration in the anterior third of the left half of the tongue. Histological investigation resulted in the diagnosis of cysticercosis. The patient was referred to an Institute for Tropical Medicine which confirmed the diagnosis serologically. CT and MR images revealed two additional lesions in the CNS. After treatment with anthelminthics these lesions in the CNS disappeared.

[Recurrent intestinal bleeding in a patient with arterio-venous fistulas in the small bowel, limited mesenteric varicosis without portal hypertension and malrotation type I]. / Rezidivierende intestinale Blutungen bei einem Patienten mit arteriovenösen Fisteln des Dünndarms, umschriebener mesenterialer Varikosis ohne portale Hypertension sowie Typ I Malrotation.

A case of vascular malformations of the small intestine associated with malrotation Type I of the right colon is reported. Representing rare conditions, vascular malformations in the small bowel are not accessible endoscopically. Therefore, gastrointestinal haemorrhage originating from this "terra incognita" is difficult to diagnose. Our patient had a medical history of anaemia of 17 years before admitted to our hospital. After a preoperative blood pool scan had evidenced the bleeding source in the proximal jejunum, the patient underwent explorative laparotomy. The bleeding source was identified and resection of a jejunal segment was performed. Intraoperatively, malrotation type I was found. Histological examination revealed angiodysplasia extending full thickness of the intestinal wall with predominance in the submucosa and serosa. Secondary arterialisation was seen in the vessels of the serosa resembling varicosis-like lesions at gross inspection. The patient did not suffer from portal hypertension. Postoperative course was uneventful and no further bleeding occurred.

[Pylephlebitis with air in the portal vein system. An unusual focus in a patient with sepsis]. / Pylephlebitis mit Luft im Pfortadersystem. Ungewöhnlicher Fokus bei einem Patienten mit Sepsis.

HISTORY AND CLINICAL FINDINGS: A 30-year-old male was transferred to the intensive care unit with worsening sepsis of unknown origin and a known history of Crohn's disease. The patient presented with a five-day history of nausea, fever, and serous diarrhea. Clinical examination of the abdomen was unremarkable except for mild epigastric pain on palpation. INVESTIGATIONS: Computed tomography (CT) of the abdomen revealed gas within the intrahepatic branches of the portal venous system, thickening of the wall of the neoterminal ileum, and mild ascites. In addition, ultrasonography showed acute thrombosis of the portal vein and the superior mesenteric vein. No wall perfusion was seen in either the neoterminal ileum or the ascending colon on color Doppler sonography. DIAGNOSIS, TREATMENT AND COURSE: Based on the combination of portal vein thrombosis along with venous gas in the portal venous system and absence of intestinal perfusion, the diagnosis of pylephlebitis with septic shock was suspected and a laparotomy was performed. Intraoperative exploration revealed phlegmonous terminal ileitis, a significant amount of cloudy fluid, and thrombosis of the mesenteric vein. A right-sided hemicolectomy with ileotransversostomy was performed. Histologic examination confirmed Crohn's disease that was associated with vasculitis and, in particular, with thrombophlebitis and subsequent transmural bowel necrosis. Antibiotic and anticoagulation therapy was resumed without further complications. CONCLUSION: In the differential diagnosis of sepsis, especially in combination with abdominal pain or gas in the portal venous system, pylephlebitis should be taken into account. Because of the high mortality, immediate further diagnostic testing and appropriate therapy of this rare diagnosis are necessary.

Heterotopic pancreatitis: gastric outlet obstruction due to an intramural pseudocyst and hamartoma.

Heterotopic pancreas, usually a silent gastrointestinal malformation, may become clinically evident when complicated by chronic inflammation. We report a case of pancreatitis and extensive pseudocyst formation in the gastric antrum, which caused gastric outlet obstruction. The diagnosis was obscured by a history of emesis during pregnancy and a previously resected gastric polyp. The nature of the obstructive lesion was not diagnosed preoperatively in spite of endosonographic evaluation. Intraoperatively, a cystic tumor of the stomach wall was found, the lesion was excised, and a pyloroplasty was performed to close the excision site. Histology revealed heterotopic pancreatic tissue with chronic inflammation, fibrosis and pseudocyst formation and adjacent to this lesion a myoglandular hamartoma. The patient is symptom-free two years after surgery and no recurrence was found. The nature of heterotopic pancreatic tissue, its diagnosis and management are discussed.

Woodchuck hepatocytes remain permissive for hepadnavirus infection and mouse liver repopulation after cryopreservation.

Isolated hepatocytes represent a relevant model of the liver and are highly required both for research and therapeutic applications. However, sources of primary liver cells from human beings and from some animal species are limited. Therefore, cryopreservation of hepatocytes could greatly facilitate advances in various research areas. The aim of this study was to evaluate whether cryopreserved primary woodchuck hepatocytes could be used for woodchuck hepatitis B virus (WHV) infection studies, and whether they could maintain their regenerative potential in vivo after thawing. Critical steps for good quality of cryopreserved hepatocytes included the use of University of Wisconsin (UW) solution as a main component of the freezing medium, stepwise reduction of dimethylsulfoxide (DMSO) to avoid osmotic shock, and maintenance of low concentrations of DMSO in the culture medium. After cryopreservation, cell viability was still high (70% to 80%), and 50% to 60% of thawed cells attached to the plates. The appearance of covalently closed circular (ccc)DNA and of WHV-replicative forms a few days after in vitro infection demonstrated that thawed woodchuck hepatocytes were still susceptible to viral infection, thus proving maintenance of a very high hepatocyte-specific differentiation status. Furthermore, transplantation of woodchuck hepatocytes into the liver of urokinase-type plasminogen activator (uPA)/recombination activation gene-2 (RAG-2) mice, a model of liver regeneration, demonstrated that cryopreserved cells retained the ability to divide and to extensively repopulate a xenogenic liver. Notably, in vivo susceptibility to infection with WHV and proliferative capacity of frozen/thawed woodchuck hepatocytes in recipient mice were identical to those observed by transplanting fresh hepatocytes.

CDw60: an antigen expressed in many normal tissues and in some tumours.

CDw60 is a recently described T-cell antigen, which functionally delivers a costimulatory signal in T-cell activation. In addition, CDw60 has been regarded as a melanoma-associated antigen. To date, only limited information exists on the distribution of CDw60 in other normal and pathologically altered tissues in human. In the present study, the expression of CDw60 was analysed immunohistologically in a large panel of formalin-fixed and paraffin-embedded normal and pathological human tissues. The antigen was detected in several normal tissues, such as epithelia of the reproductive system, exocrine and endocrine glands, glial cells and neurons of the central and peripheral nervous systems, and lymphoid cells. These showed different subcellular distribution patterns, i.e. (1) cell surface labelling of peripheral lymphocytes and lymphocytes of the lymph node and thymus, (2) diffuse cytosolic staining in lymphocytes, subpial glial processes, and the outer plexiform layer of the retina, (3) granular cytoplasmic staining associated with the Golgi apparatus in epithelial cells of certain endocrine and exocrine glands, of the ductus epididymis and deferens, neurons of the peripheral and central nervous system, and lymphocytes and megakaryocytes of the bone marrow. In exocrine glands, e.g. of the prostate and uterine corpus, CDw60-positive Golgi fields were located in the juxtaluminal cell compartment, thus reflecting a polarized distribution. In some malignant tumours, the neoplastic cells contained CDw60-immunolabelled Golgi complexes, which were disorderly distributed throughout the cytoplasm, thus reflecting a loss of epithelial polarity. Only in mammary carcinomas was abnormal cell surface labelling detected. A putative de novo expression of CDw60 was observed in pleomorphic adenoma and mucoepidermoid carcinoma of the parotid gland, seminoma, embryonal and teratocarcinoma of the testis, small cell carcinoma of the lung, and malignant melanoma. These results define the CDw60 determinant as a broadly distributed antigen within a large panel of normal human tissues. The antigen is also detectable in some previously undescribed benign and malignant tumours, which may give importance to CDw60 as a possible diagnostic marker.

A transgenic mouse model for the ductal carcinoma in situ (DCIS) of the mammary gland.

The ductal carcinoma in situ (DCIS) of the mammary gland represents an early, pre-invasive stage in the development of invasive breast carcinoma and is increasingly diagnosed since the introduction of high-quality mammography screening. Uncertainties in the prognosis for patients with DCIS have caused a controversial discussion about adequate treatment, and it is suspected that most patients undergoing mastectomy may be overtreated. In order to improve treatment and treatment decision, it therefore is highly desirable to identify prognostic markers and therapeutic targets for DCIS. We here introduce a set of transgenic mice (WAP-T and WAP-T-NP lines) presenting with various morphological forms of DCIS-like lesions. In these mice the SV40 large tumor antigen is specifically induced in epithelial cells of the terminal duct lobular units (TDLU). As a consequence of continuous expression of the oncogene, the animals develop multifocal DCIS and consequently invasive carcinoma within strain specific periods of latency. DCIS lesions in transgenic mice exhibit distinct architectural and cytological features which closely resemble those commonly present in humans. We therefore propose these transgenic lines as an experimental model to study the underlying molecular events leading to DCIS and its progression to invasive disease.

Umbilical endometriosis.

Cutaneous endometriosis is a well known but rare phenomenon. We present a case of spontaneous umbilical endometriosis. The patient revealed a polypoid, brown-blue nodule within the umbilical depression with the typical history of monthly bleeding from the umbilicus. The differential diagnoses are summarized.

Breast tumors with myofibroblastic differentiation: clinico-pathological observations in myofibroblastoma and myofibrosarcoma.

This report describes the clinico-pathological features of myofibroblastic tumors of the breast in six patients. Four women and one man presented with a benign myofibroblastoma. The sixth patient was a woman with myofibrosarcoma. All myofibroblastomas were composed of a fascicular arrangement of spindle cells embedded in dense bundles of collagen. Tumors differed with respect to their proportion of neoplastic cells and collagenous stroma as well as cellular pleomorphism. Based on this variation, the tumors could be subclassified as classic, collagenized, epithelioid and cellular myofibroblastoma. Immunohistological staining confirmed myofibroblastic differentiation by strong expression of either desmin or smooth muscle actin with coexpression of vimentin. In addition, numerous cells reacted with antibodies to CD68. Proliferative activity was rather low in the myofibroblastoma with an average of 0-2 mitotic figures per 10 HPF. DNA cytometric analysis was performed in two cases and showed diploid stem lines with minor S-phase fractions (1% and 3%). In the myofibrosarcoma, cells contained pleomorphic nuclei with some giant cells and numerous mitotic figures (6-7/10 HPF) and had infiltrating margins that were apparent even grossly. Immunohistochemically, tumor cells strongly expressed vimentin, smooth muscle actin and fibronectin. Ultrastructurally, neoplastic cells met the criteria of myofibroblasts, i.e. contained abundant intermediate filaments and myofilament bundles with focal densities as well as fibronexus junctions. DNA cytometric analysis exhibited again a diploid stemline but marked proliferative activity was present as indicated by an S-phase fraction of 20%. In conclusion, in benign myofibroblastoma there may be some cellular pleomorphism but mitotic activity is always low. The malignant counterpart, myofibrosarcoma, is characterized by marked cellular pleomorphism, infiltrating margins and high mitotic rate.

Changed expression of 9-O-acetyl GD3 (CDw60) in benign and atypical proliferative lesions and carcinomas of the human breast.

Expression of gangliosides is affected in various ways by malignant cell transformation. In the present study, we investigated the expression of CDw60, a constituent of O-acetylated disialogangliosides, in benign and atypical proliferative breast diseases, and preinvasive and invasive carcinomas by immunohistochemistry and thin-layer chromatography (TLC). In normal ducts, antibodies to CDw60 (mAb M-T21) reacted to membranes of the Golgi apparatus in the juxtaluminal cell compartment. A similar polarized distribution of Golgi cisterns in epithelial cells was observed in several benign lesions, i.e., fibroadenomas, intraductal papillomas, and gynecomastia. In contrast, blunt duct adenosis and duct hyperplasia exhibited an abnormal cytosolic and cell surface staining, whereas atypical duct hyperplasia showed randomly dispersed immunoreactive Golgi cisterns, indicating loss of epithelial polarity. In mammary carcinomas and in two breast carcinoma cell lines (MCF-7 and EFM-19) the neoplastic cells contained CDw60-immunolabelled Golgi complexes, which were distributed in a disorderly fashion throughout the cytoplasm, thus reflecting a loss of epithelial polarity. Additionally, only well differentiated ductal carcinomas in situ or invasive ductal carcinomas disclosed a strong cell surface labelling, which was absent in lower differentiated carcinomas of the same types. In all carcinomas, the intensity of CDw60 immunostaining decreased with progressing loss of differentiation (grade of dedifferentiation), as demonstrated by staining intensity in paraffin sections and by evaluation of the relative amounts of extracted 9-O-acetyl GD3 by TLC. Our results indicate that abnormal CDw60 expression is already detectable in benign proliferative breast lesions with different risk rates to develop into malignant lesions. Downregulation of CDw60 expression in poorly differentiated invasive carcinomas may be the consequence of loss of cell functions usually associated with poor prognosis.

Fate of developing astrocytes in the optic nerve of the myelin-deficient rat.

There is considerable debate on the development of a glial cell line in the rat optic nerve, which is characterized by the specific expression of the A2B5 and HNK-1 epitopes. This cell line has been assumed to give rise to oligodendrocytes and so-called type 2 astrocytes. However, it is doubtful that the latter cell type really exists in vivo. In the present study, we have addressed this question by investigating the development of astrocytes in the myelin-deficient (md) rat, which is characterized by dysmyelination and loss of oligodendrocytes. Defective oligodendrocytes were observed by the third postnatal day, well before the generation of type 2 astrocytes. Consequently, the number of type 2 astrocytes was reduced in cultures prepared from optic nerves of md rats vs. controls. This finding was not paralleled in vivo; i.e., no dying astrocytes were observed in md sections by conventional electron microscopy. However, immunoreactivity against the HNK-1 epitope was enhanced in md compared to control sections. Ultrastructurally, HNK-1 immunoreactivity was detected predominantly on the axonal surface at astroaxonal contact sites, which were found only at the nodes of Ranvier within controls but extended to the whole axonal surface in md animals. Only a minor portion of the immunoreactivity derived from glial cells, presumably from oligodendrocytes at the paranodal region in controls. Thus, the HNK-1 epitope is not a useful antigen for distinguishing astrocytes in the rat optic nerve. Accordingly, our results do not provide evidence for the existence of specialized type 2 astrocytes in vivo. In vitro, these cells are probably only oligodendrocytes that mimic some astroglial features if grown in serum-containing media.

CD15-containing glycoconjugates in the central nervous system.

CD15-containing glycoconjugates have a common trisaccharide residue, 3-fucosyl-N-acetyllactosamine, which can be recognized by a panel of monoclonal antibodies. Immunohistochemical studies revealed a widespread distribution of CD15 in several epithelial non-neural tissues as well as in the CNS. In the mature mammalian brain CD15-containing glycolipids and glycoproteins are constantly present in astrocytes, whereas oligodendrocytes and particular subpopulations of neurons are variably immunostained. CD15 immunoreactive astrocytes are spatially distributed in some brain regions, which points to specialized functions of astroglial subpopulations. The expression of CD15 follows a timely ordered pattern during the development of glial cells and neurons of certain brain areas, such as the human and rat cerebellum and the mouse visual system. During morphogenesis, CD15 may exert either growth-promoting or growth-repulsive activities to guide cell migration. In CNS lesions altered expression patterns of CD15 may occur. For example, in human gliomas the staining intensity for CD15 inversely correlates with the grade of malignancy. In degenerative brain diseases reactive astrocytes may reveal an increased labelling intensity on their cell surface as well as an abnormal cytosolic accumulation of the epitope. The functional significance of CD15 in the CNS is not exactly known yet. The carbohydrate could be involved in cellular adhesion and/or as receptor molecule in signal transduction pathways, as has recently been demonstrated for leukocyte-platelet or leukocyte-endothelial cell interactions.

Hereditary compulsive self-mutillating behaviour in laboratory rabbits.

During the last few years an increasing number of cases of extensive automutilation has been observed in a rabbit breeding colony of Checkered crosses. Digits and pads of the front feet were traumatized. No other behavioural abnormalities or signs of disease were evident. Self-mutillation was seen both in stock, breeding and experimental animals, in rabbits kept singly in cages and in those housed in groups on the ground, in rabbits kept in different buildings and under the care of different staff members. This behavioural abnormality of Checkered crosses has also been observed in animals after being placed into other institutions or private homes. No evidence of an agent responsible for the occurrence of self-injury could be found with parasitological, mycological, histological, clinical or haematological examination. Twelve to 16 animals are affected yearly in a colony varying in size between 130 and 230 rabbits. Following complete healing, relapses occurred up to 3 times per year, on either the same or the opposite front foot. In the last 21 cases episodes of automutillation could be regularly interrupted with the dopamine antagonist, haloperidol. Similar signs of auto-mutillation were never seen in animals of another breeding line kept in the same building and under the same conditions nor in animals brought in from other breeding colonies. A relatively high coefficient of inbreeding can be presupposed in this 15-year-old breeding colony of Checkered crosses. A genetic predisposition for the behavioural anomaly described appears very likely.

Gliomatosis peritonei combined with mature ovarian teratoma: immunohistochemical observations.

Gliomatosis peritonei (GP) is the metastatic implantation of glial cells within the peritoneal cavity of patients with ovarian teratomas. The case of a young woman is presented, who initially developed a mature teratoma in the left ovary that was surgically removed. Nine years later a mature teratoma in the right ovary was excised, upon which GP was found in the greater omentum. To identify the cellular composition of the ovarian teratoma and of the omental implants, immunostainings were performed using antibodies against glial and neuronal antigens as well as against determinants of hematopoietic cells. In the teratoma the neuroectodermal part was strongly HNK-1-positive and contained GFAP- and vimentin-positive astrocytes and some NSE-positive neuron-like cells. In addition, neuroectodermal tissue was infiltrated by numerous CD68-positive macrophages/histiocytes and CD20-positive B lymphocytes. The omental nodules consisted of astrocytes, which expressed GFAP, vimentin and desmin. The implants also contained macrophages/histiocytes, which exhibited morphologic features reminiscent of microglial cells. In GP, macrophages might release glia-promoting trophic factors, which could allow the neural component of ovarian teratoma to implant in the peritoneal cavity and survive there for many years. Macrophage-derived factors might induce astroglial differentiation, which could explain why the peritoneal implants are mostly mature even when they originate from immature teratomas.

The carbohydrate epitope 3-fucosyl-N-acetyllactosamine is region-specifically expressed in astrocytes of the rat brain. Light- and electron-microscopical observations.

The carbohydrate epitope 3-fucosyl-N-acetyllactosamine (CD15) is involved in cell-to-cell recognition processes in various tissues. In the CNS of the adult rat, immunoreactivity for CD15 reveals a region-specific distribution pattern by light microscopy. In the present study we investigated the ultrastructural localization of CD15 in the rat brain using preembedding immunocytochemical methods. In addition we studied CD15 expression in cultured astrocytes from optic nerves of 11-day-old rats. In optic nerve sections, immunostaining was found on the surface of astrocytes at various contact sites, i.e. astrocyte-astrocyte, astrocyte-oligodendrocyte, astrocyte-axon myelin, and astrocyte-blood vessel contacts. Oligodendrocyte-oligodendrocyte contacts, however, were always negative. In the telencephalic cortex, CD15 immunoreactivity was found in glial cell processes around synapses and in the cerebellar cortex in Bergmann glial cells. In astrocytes grown in serum-containing medium, CD15 was expressed on the surface of fibroblast-like glial fibrillary acidic protein-positive astrocytes, which were identified as type 1 astrocytes as well as on process-bearing A2B5-positive cells, representing type 2 astrocytes. The present data support the assumption that in the adult rodent brain, CD15 is exclusively expressed by astrocytes. The in vivo distribution of this carbohydrate molecule on distinct astroglial contact sites supports the notion that CD15 could act in cell-to-cell recognition processes.

Visualization of axonal degeneration after optic nerve lesion in rat by immunohistochemical labelling for myelin basic protein (MBP).

Immunohistochemical staining of myelin basic protein (MBP) was followed during axonal degeneration of rat retinal fibers within the first 3 weeks after injury. Wallerian degeneration of rat retinal fibers was elicited by unilateral transection or crush injury of optic nerve. MBP-labelled fibers in central retinal pathways and visual nuclei showed sequential changes of the myelin sheath, such as swelling at 1-2 days post lesion (dpi), granular staining at 4-8 dpi, and granular debris formation at 21 dpi. Consequently, immunostaining for MBP could be used to identify early stages of degenerating myelin and persisting myelin debris which is known to contain neurite growth inhibitors.