Histochemical studies on striated muscle of ischemic and angiosurgically reperfused lower extremities

There have been reports on an increased oxidative capacity in muscle tissue from the diseased legs of patients with intermittent claudication. In biopsy from specimens the gastrocnemius muscle of 25 patients the effect of arterial reconstructive surgery were studied, using fresh frozen cryostate sections and histochemical reactions for some oxidoreductases. The present study describes additional histochemical changes in the leg muscles in patients suffering from arterial insufficiency. The changes observed are correlated to the clinical severity of the disease.     

Immunohistochemical and molecular analysis of p53, RB,and PTEN in malignant peripheral nerve sheath tumors

The molecular basis of both sporadic and neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNSTs) is yet largely undetermined. Therefore, we analyzed a series of 12 MPNSTs - including two cases which arose in the setting of NF1 - for molecular alterations in the p53, retinoblastoma ( Rb), and PTEN tumor suppressor genes. Furthermore, the immunohistochemical expression of p53, RB, and PTEN protein was examined in these tumors. One mutation (8%), an A to T transversion leading to an amino acid exchange, was found in exon 5 of the p53 gene in a sporadic MPNST. In two other sporadic tumors (20%), loss of heterozygosity (LOH) of the p53 gene occurred. Nuclear overexpression of p53 protein was observed in ten tumors (83%). Loss of RB protein expression was seen in two MPNSTs (17%), and LOH of the Rb gene was detected in four tumors (44%), including the two NF1-associated MPNSTs, one of them showing concomitant loss of RB protein expression. No mutation in the PTEN gene was detected, and cytoplasmic immunoreactivity for the PTEN protein was maintained in eight MPNSTs (67%). We suggest that alterations in the p53 and RB pathway, both are essential in controlling the cell-cycle progression, are critical points in the tumorigenesis of sporadic and NF1-associated MPNSTs, whereas the PTEN gene seems to play no significant role in this process.     

Transvenous parasympathetic nerve stimulation in the chronic myocardial infarction phase

The study describes the electrophysiological effects of transvenous cardiac nerve stimulation in an animal model of myocardial infarction. In ten sheep with recent myocardial infarction, transvenous stimulation of parasympathetic cardiac nerves was achieved from a catheter in the right pulmonary artery. The effects of transvenous cardiac nerve stimulation on sinus rhythm cycle length, ventricular refractory periods and inducibility of monomorphic ventricular tachycardia were evaluated. Sinus rhythm cycle length increased from 620 +/- 24 ms to 723 +/- 30 ms during nerve stimulation with 20 Hz and to 779 +/- 28 ms during stimulation with 40 Hz (p < 0.05). Effective ventricular refractory periods from stimulation sites in non-infarcted right and left ventricular myocardium showed a tendency towards prolongation during cardiac nerve stimulation with shortening after cessation of stimulation. These differences, however, were not significant. In contrast, refractory periods from stimulation sites within the infarcted area remained unchanged during cardiac nerve stimulation. The inducibility of monomorphic ventricular tachycardia by programmed electrical stimulation was reduced during transvenous cardiac nerve stimulation. Pathological examination showed cholinergic nerves in close proximity to the tip of the stimulation catheter in the right pulmonary artery. Transvenous cardiac nerve stimulation in sheep with remote myocardial infarction exhibits electrophysiological effects on the ventricles. Although a parasympathetic effect on the ventricles could not be proven, the observed effects may result from direct stimulation of efferent parasympathetic nerves.     

Expression of transforming growth factor-beta receptor type 1 and type 2 in human sporadic vestibular Schwannoma

Expression of the transforming growth factor-beta (TGF-beta) protein family in the peripheral nervous system is well established, but the role of their cognate receptors TGF-beta receptor type 1 (R1) and type 2 (R2) has been less well studied. TGF-beta plays an essential role in Schwann cell proliferation and differentiation, and is involved in neurotrophic effects of several neurotrophic substances. TGF-beta is also expressed in benign peripheral nervous system tumors such as vestibular schwannomas. In the present study, we aimed to detect TGF-beta R1 and R2 in a total of 40 sporadic vestibular schwannomas using immunohistochemistry, and correlated the findings to essential clinicopathologic data. TGF-beta, TGF-beta R1, and TGF-beta R2 mRNA was further analyzed by RT-PCR in six vestibular schwannomas. TGF-beta R1 immunoexpression was found in about 95% of the tumors. TGF-beta R1 was equally present in Antoni A and Antoni B areas of the tumors. TGF-beta R2 was found immunohistochemically in 77%. In addition, all tumors showed strong expression of TGF-beta. No correlation between TGF-beta R1 or R2 expression and clinicopathologic parameters such as age, sex, clinical symptoms, growth pattern, and proliferation acitivity as measured by Ki-67 (MIB-1) staining was found. Moreover, all schwannomas studied contained TGF-beta, TGF-beta R1, and TGF-beta R2 mRNA. Therefore, the TGF-beta/TGF-beta R1 and -R2 system is present in human schwannomas, but its biologic role for tumor development and growth remains unclear.     

Primary primitive neuroectodermal tumor of the spinal cord: case report and review of the literature.

We present the clinical, radiological, and pathological features of a primary primitive neuroectodermal tumor (PNET) that occurred in the thoracic spinal cord of a 69-year-old man. Magnetic resonance imaging (MRI) demonstrated on T1-weighted images a 2x1x5 cm isointense intraspinal mass with homogeneous contrast enhancement extending from the C7 to the Th3 level. There was no clinical or radiological evidence for the existence of an intracranial tumor. Histological examination revealed a small round cell tumor with rosette formation and immunohistochemical characteristics of a PNET. The patient is the oldest among the 20 cases with this rare spinal cord neoplasm reported so far in the literature; the previously published cases are briefly reviewed.     

Analysis of TP53 and PTEN in gliomatosis cerebri

Gliomatosis cerebri (GC) is a rare glial neoplasm with extensive diffuse brain infiltration but relative preservation of the underlying architecture. Previous molecular studies, mostly analyzing biopsy samples, have suggested an astrocytic origin of GC, but a larger collective of autopsy tissue has not been investigated so far. Furthermore, whether the widespread neoplastic infiltration is based on a monoclonal process is still a matter of debate. In the present study, we screened paraffin-embedded brain tissue from different areas of 18 cases (8 autopsy cases and 10 biopsies) for alterations in the TP53 and PTEN genes. Nuclear accumulation of p53 protein was detected in 9 cases (50%). Somatic TP53 mutations occurred in two autopsy cases (11% of all cases). In the first case, a C-->T transition in codon 273 (Arg-->Cys) was detected in all tumor samples. In the second case, in tumor samples from one hemisphere, nuclear accumulation of p53 was caused by a G-->A transition in codon 244 (Gly-->Asp). In the present series, no mutations within the coding region of PTEN were found. Pten expression was observed in two autopsy cases (25%) and seven biopsy samples (70%). These data suggest that TP53 is affected in some cases, but other yet-unidentified genetic alterations might contribute to tumorigenesis in GC. Furthermore, although GC might be a monoclonal process, the presence of different tumor clones cannot be ruled out.     

Long-term survival of glioblastoma multiforme: importance of histopathological reevaluation

The overall prognosis for patients with glioblastoma multiforme is extremely poor. However, a small proportion of patients enjoy prolonged survival. This study investigated retrospectively the extent to which erroneous histopathological classification may contribute to long-term survival of patients initially diagnosed with “glioblastoma multiforme”. We compared two age- and gender-matched patient groups with different postoperative time to tumor progression (TTP), defined as “short-term” for TTP of less than 6 months (n=54) and “long-term” for TTP of more than 12 months (n=52). Histological specimens of the corresponding tumors, all primarily diagnosed as glioblastome multiforme, were reevaluated according to the current World Health Organization (WHO) classification of central nervous system tumors, with the investigators being blinded to clinical outcome. Among the tumors from short-term TTP patients, one tumor (2%) was reclassified as anaplastic oligoastrocytoma (WHO grade III) while the remaining 53 were confirmed as glioblastoma multiforme. In contrast, 13 tumors (25%) from the long-term TTP patients were reclassified, mostly as anaplastic oligodendroglioma (WHO grade III; n=7) or anaplastic oligoastrocytoma (WHO grade III, n=2), respectively. In addition, three were reclassified as anaplastic astrocytoma (WHO grade III), and one was identified as anaplastic pilocytic astrocytoma (WHO grade III). Our data indicate that a sizable proportion of glioblastoma patients with long-term survival actually carry malignant gliomas with oligodendroglial features. The correct histopathological recognition of these tumors has not only progrostic but also therapeutic implications, since oligodendroglial tumors are more likely to respond favorably to chemotherapy. Received: 9 November 1999, Received in revised form: 13 January 2000, Accepted: 3 February 2000     

Histochemical-morphometric studies of skeletal muscles in advanced arterial circulation disorders of the extremities

Biopsies of M. gastrocnemius and Nervus suralis of 12 patients with advanced disturbances of circulation were examined by means of morphometrical and histochemical methods. The histological picture of a neurogenic atrophy of the muscle fibres with partially strong hypertrophy of the slow-twitch fibres was found. The main reaction patterns and the pathogenetic mechanisms are discussed. Alterations in the ratio of type I and type II fibres are described. Fiber type disproportions, i.e. more than 75% type I fibres, may suggest that in hypoxia the type II fibres are more intensely damaged than type I fibres. There are correlations between pathological fibre distribution and the success of vasosurgical treatment.