Degrees of malignancy in human primary central nervous system tumors: ornithine decarboxylase levels as better indicators than adenosylmethionine decarboxylase levels.

The levels of activity to ornithine decarboxylase (ODC) and adenosylmethionine decarboxylase (AMD) were measured in various types of primary human tumors of the central nervous system (CNS) and whenever possible were related to the malignancy of the tumor graded according to histopathologic criteria. In astrocytomas ODC levels increased linearly and progressively from infratentorial pilocytic astrocytoma (grade I) to glioblastoma multiforme (grade IV) and corrected well with the degree of histologic malignancy of the tumor. AMD activity levels, however, correlated with tumor malignancy only up to grade III astrocytoma. Medulloblastomas exhibited an unusual dichotomy with regard to the levels of polyamine biosynthetic decarboxylases (PBD): Medulloblastomas had the highest ODC activities of all the CNS tumors tested but had low AMD activities. In tumors of neuroepithelial tissue ODC level increases and, when present, AMD level increases were not due to proliferation of new blood vessels, because CNS hemangioblastomas had very low levels of both PBD activities. No significant differences in either of the PBD levels were observed among the several variants of meningiomas tested, the meningotheliomatous, the transitional, and the fibrous meningiomas. However, atypical forms of meningioma, i.e., those with mitotic figures, whatever the histologic variants, had higher levels of ODC, but not of AMD, than the typical forms, i.e., those without mitotic figures.

Size reduction of macroprolactinomas by bromocriptine or lisuride treatment.

We have administered to 29 patients with macroprolactinoma the dopamine agonists bromocriptine and lisuride for 1-50 months (mean +/- SE, 12.7 +/- 1.8) in order to assess the effects of these drugs on tumor size. Fourteen patients were treated with bromocriptine (dose range, 7.5-20 mg/day), 12 patients were treated with lisuride (0.6-2 mg/day), and 3 patients were given both drugs. Computed tomography performed before and during treatment showed the occurrence of tumor shrinkage in 18 patients (62%), but in no case was a complete disappearance of the tumor observed. In 5 of these patients, it was even possible to document tumor shrinkage within the first month of treatment with low doses of the dopamine agonists, whereas in other patients, tumors shrank only after prolonged treatment with higher doses. Visual field and acuity improved or normalized in 8 of the 13 patients with visual defects; in some cases, the improvement was reported as early as 2 days after the treatment was started. Plasma PRL levels fell in all patients who showed a reduction in tumor size; in 2 other patients, PRL levels were only poorly suppressed, and tumor size remained unchanged. In the remaining patients, PRL levels were lowered without convincing evidence of tumor shrinkage. In considering the high percentage of patients showing tumor shrinkage under medical treatment, we propose a course with dopamine agonists as the first step in the management of patients with macroprolactinomas regardless of the presence of visual impairments.

The Fab region of IgG2 human myeloma proteins does not bear the streptococcal protein G-specific determinant.

Seven out of ten Fab (F(ab')2/Fab') preparations derived from purified human myeloma IgG showed a substantial binding to protein G-Sepharose. Subclass analysis revealed that the 7 protein G-reactive Fabs included 3 IgG1, 2 IgG3 and 2 IgG4 Fabs, whereas the remaining 3 which were not adsorbed were IgG2 Fab. Incubation of protein G-Sepharose with non-saturating amounts of 4 Fab preparations, representative of all IgG subclasses, showed that gamma 1, gamma 3 and gamma 4 Fabs adsorbed from 26 to 28.3%, whereas 80% of gamma 2 Fab was left in the supernatant after adsorption. These results indicate that human IgG2 lack PG-specific Fab-associated reactive site(s).

Serum levels of beta-2-microglobulin-free heavy chain of HLA class I antigen in healthy individuals: relationship to their class I allotype.

An ELISA-based double determinant immunoassay has been established to measure the soluble beta2-microglobulin (beta2m)-free heavy chain (FHC) of the HLA-B, -C (and HLA-A3, -A28 and -A30) class I molecular complex in sera from 212 HLA-typed healthy unrelated individuals. FHC was calculated by means of a standard curve constructed using serial concentrations of beta2m-associated HLA-class I heavy chain (HLA-I)/FHC purified from cultured human lymphoid cell C1R-sB7-supernatant. The mean FHC concentration (+/-SD) was 0.25 mg/l (+/-0.2). Its median concentration did not statistically differ between males and females, though the male/female ratio was greater in the high secretor (FHC >0.45 mg/l; mean + 1SD) than in the low secretor group (FHC < 0.05 mg/l; mean - 1SD). FHC < 0.05 mg/l was statistically (Fisher's exact test) associated with HLA-B17 (p = 0.003); FHC > 0.45 mg/l was statistically associated with HLA-B35 (p = 0.003) and -Cw4 (p = 0.002). None of these allele-positive groups showed a mean FHC concentration 1.5 times higher than that of the corresponding allele-negative ones. This allotype-dependent HLA-B and C FHC enhancement was less marked than that previously reported for HLA-I in individuals carrying HLA-A9 (and its splits). These results indicate that FHC could be a more valuable marker when its levels are compared among individuals carrying different allotypes. Moreover the lack of correlation between FHC and HLA-I levels measured in 52 HLA-A3, -A28 or -A30 positive individuals suggests that the two molecules may be regulated by different metabolic pathways and their serum expression may have a different biological significance.

Angiography and computerized tomography in the diagnosis of aneurysmal bone cyst of the skull: case report.

An aneurysmal bone cyst of the occipital bone, presenting as an intracranial space-occupying lesion, is reported. Clinical and neuroradiological findings are described in detail. The significance of angiographic and computerized tomographic findings is discussed.

Artificial lamina-assisted laminoplasty performed in seven cases.

OBJECT: The authors attempted to simplify the operative approach to severe multilevel cervical spondylotic myelopathy. Seven patients with progressive and severe myelopathy underwent modified double-door laminoplasty during a 5-month period. METHODS: The double-door laminoplasty procedure was modified by using two artificial titanium laminae obtained by simple surgical 0.5-mm Ti-mesh (rather than by bone graft or ceramic spacers). Preoperatively, gait disturbance was present in all patients with long-tract signs on neurological examination. In all cases the sagittal diameter of the cervical spinal canal was somewhat reduced (< 10 mm) by congenital stenosis, and further severe compression of the spinal cord resulted from osteophytic bars and calcified ligamenta flava at different levels. No abnormal alignment, pathological movements, or instability was present. Computerized tomography (CT) studies demonstrated severe multilevel cervical compression, and T2-weighted magnetic resonance (MR) imaging demonstrated pathological areas of hyperintensity within the spinal cord in all cases. In the initial follow-up study (range 8-12 months), the patients who underwent this procedure experienced marked improvement of gait disturbance without any significant incidence of morbidity or complications. Postoperative CT and MR imaging studies demonstrated complete spinal cord decompression and restoration of the patency of the subarachnoid spaces. CONCLUSIONS: The proposed procedure has the advantage of achieving both an immediate stabilization of the open laminae by means of a bridgelike mechanism and protection from the possible compression of the dural sac by paravertebral muscles.

Anti-CD4 monoclonal antibody (mAb) and anti-idiotypic mAb to anti-CD4 in the therapy of autoimmune diseases.

The present report critically reviews the rationale, experimental and clinical effectiveness and limits of anti-CD4 monoclonal antibody (mAb) therapy. References are also made to a novel approach involving active immunotherapy and an anti-idiotypic mAb bearing the internal image of human CD4 antigen. Preliminary observations concerning the effects of this treatment in one patient with rheumatoid arthritis and in one patient with systemic lupus erythematosus are reported.

Human CD4 internal antigen anti-idiotypic monoclonal antibody. immunochemical and sequence analysis.

The mouse mAb2 16D7 recognizes the paratope of the syngeneic anti-human CD4 mAb HP2/6 (mAb1 of our idiotypic cascade) and mimics CD4 in xenogeneic settings in humans. Immunochemical and sequence analyses were performed to define the minimum structural requirement for this mimicry. Binding assay of mAb1 with isolated naive 16D7 H and L chains showed that only the second reacted with mAb1. Specificity was indicated by the lack of reactivity of mAb1 with the L chain of mAb2 14D6, which also recognizes mAb1-paratope. It is likely that the 16D7-L mAb1-specific epitope is "sequence-dependent", since fully denatured 16D7-L still reacted with mAb1. Sequence analysis of 16D7 and mAb1 showed a high degree of homology of their VH. as both were coded by the same gene family (V/II), whereas CDR3 showed the greatest diversity. Alignment of 16D7-H CDR3 with CD4, however, produced no similarity. In contrast, analyses of the 16D7 VL sequence (XX/V) defined a CDR3 6-mer peptide with a 50% identity (83% of similarity) to the CD4 stretch 218-223. This peptide seems a suitable replacement for 16D7 in active immunotherapy as it did not match any protein fragment retrieved from the n-r database (NCBI) and both the peptide and the corresponding CD4 amino acid stretch are surface accessible. Based on their immunochemical profiles and similarity to CD4, four additional 16D7-derived peptides were designed for synthesis. The data indicate that CD4 mimicry by mAb2 can be obtained at the level of primary structure and provide useful information for the synthesis of peptide(s) with bioactive potential.

The surgical approach to intraorbital tumors in children.

A series of 20 children operated for intraorbital tumors is presented. Ten of the patients were operated by the lateral approach, requiring orbitotomy in only 4 cases. Ten patients were operated by the medial transcranial transfrontal exposure. The surgical approach is mainly related to the location of the tumor, regardless of its malignancy. The relevance of the different neuroradiological procedures and the advantages of the different surgical approach are discussed.

Monoclonal antibodies in the immunotherapy of autoimmune diseases.

The present report critically reviews the rationale, clinical effectiveness and limits of monoclonal antibody-based immunotherapy in the treatment of autoimmune diseases, with particular emphasis on tumor necrosis factor-alpha blocking reagents. Reference will also be made to active immunotherapy whereby an endogenous response induced by anti-idiotypic monoclonal antibodies or peptides toward molecules regarded as passive immunotherapy targets, is expected to mediate the therapeutic effects.

Glioblastoma multiforme of the cerebellum: description of three cases.

Only 43 cases of glioblastoma multiforme of the cerebellum have been reported in the literature. This report is based on the findings of 3 cerebellar glioblastomas in a review of 1,206 consecutive confirmed cases of glioblastoma operated on between 1947 and 1977 at the Istituto Neurologico of Milan, giving an incidence of 0.24%. Clinical features are similar to those of any other fast-growing subtentorial tumour. Neuroradiological studies, including CAT, are of little help in predicting the exact nature of these tumours before surgery. A correct diagnosis can be reached only by microscopic examination. Histological patterns appear in no way to differ from those of cerebral glioblastoma. The biological behaviour of these tumours is in all respects identical to that of glioblastoma of cerebral hemispheres.

Interfascicular suture with nerve autografts for median, ulnar and radial nerve lesions.

Interfascicular nerve suture with autografts is the operation of choice for repairing peripheral nerve injuries because it ensures more precise alignment of the fasciculi and so better chances of reinnervation of the sectioned nerve. The procedure as described by Millesi et al has been used at the Istituto Neurologico di Milano in 30 patients with traumatic lesions of the median, ulnar and radial nerves. All have been followed up for 2 to 7 years since operation. The results obtained are compared with those of other series obtained with interfascicular suture and with epineural suture. Microsurgery is essential. The best time to operate is discussed.

Absence of streptococcal protein G (PG)-specific determinant in the Fab region of human IgG2.

It has been previously reported that CH1 Fab protein G-contact site is responsible for the widespread recognition of mouse and human IgG Fab by PG. Here we present evidence that PG binding to F(ab')2 is restricted, as indicated by the lack of reactivity with PG-Sepharose columns of a portion of F(ab')2 fragments obtained by pepsin digestion of human IgG from a commercial immunoglobulin preparation for intravenous use or purified from sera of two healthy blood donors and two patients with polyclonal hypergammaglobulinaemia. Isoelectric focusing showed that F(ab')2 fragments that did not bind PG focused in a lower pH range compared with those which did. Testing of the Fab fractions with MoAbs to kappa and lambda light chains or to gamma1, gamma2 and gamma3-Fab subclass determinants showed that gamma2-F(ab')2 were mainly found in the PG non-reactive F(ab')2 fraction, and that this distribution was not influenced by the L chain isotype. These results indicate that the PG-specific binding determinant(s) is not expressed in the F(ab')2 region of most human IgG2.

Intracranial repair of interrupted facial nerve in course of operation for acoustic neurinoma by microsurgical technique.

The microsurgical refinement of the lateral suboccipital approach is, in our opinion, the most satisfactory operative technique for achieving total removal of acoustic neurinomas of all sizes. In this series of 164 operated cases, large or very large tumours accounted for 64% of the cases (105 patients). The facial nerve was sacrificed in about 19% of the cases. In 81% of the cases the facial nerve was respected (65%) or repaired (16%) by direct intracranial suture performed immediately after tumour removal. Good or fair functional results were obtained in about 65% of the cases by this last procedure, which has to be considered as the treatment of choice for facial nerve repair. The results are compared with those of other series and with those obtained by different nerve substitution procedures.

Natchev's auto-traction for lumbago-sciatica: effectiveness in lumbar disc herniation.

In Lind's auto-traction (LAT) for lumbago-sciatica, the patient provides traction force by pulling with the arms on a specially designed table, which also allows painless mobilization of the lumbar spine and passive traction. Two studies reported that one to 15 one-hour sessions on successive days might be sufficient to relieve pain in 25% to 90% of cases with verified lumbar disc herniation. Unfortunately, the technique imposes tiring manual efforts on the therapist and requires that the patient be transported by ambulance and confined to bed for a long time. These inconveniences were removed in a new version of the treatment proposed by Natchev. The effectiveness of Natchev's auto-traction (NAT) was evaluated in an open prospective trial on 77 patient with chronic lumbago-sciatica refractory to previous therapies, and herniation of one or more lumbar discs verified by computed tomography (CT) or myelography. Thirty-six of the 77 patients (47%) responded to the treatment in three to ten (median = 5) half-hour sessions. Pain intensity dropped to 27% (median) of the pretreatment intensity. Six months after treatment, 28 of the 36 responders were stable; only four had undergone surgery. By contrast, 20 of the 41 nonresponders had been operated on. The severity of either the radiologic or the neurologic picture was not predictive of the outcome. NAT was as effective as LAT: thus, due to its greater convenience it appears to be suitable as a routine approach in lumbar disc herniation and as a screening technique before surgery.

Beta-2 microglobulin-free HLA class I heavy chain (FHC) A3 and/or A30 soluble products contribute only minimally to serum FHC expression.

No monoclonal antibodies (mAbs) are presently available to measure the total amount of beta2-microglobulin-free HLA class I heavy chain (FHC) in sera. The available ELISA-based double determinant immunoassay (DDIA), established to measure FHC, uses two mAbs (TP25.99 and HC-10) that recognize a monomorphic determinant expressed on all HLA-B/C FHC products and a determinant expressed only on some HLA-A FHC products. This restricted reactivity implies that, in addition to HLA-B/C, HLA-A FHC products are also detected in individuals bearing HLA A3 and/or A30 allotypes. The aim of this study was to establish whether such restriction results in the detection of low FHC levels in individuals lacking HLA A3 and/or A30 allospecificities. The FHC mean concentration (+/- SD) in 294 healthy blood/bone marrow donors (HBDs) was 0.24 (+/- 0.2) mg/l. The grouping of HBDs according to their HLA-A FHC product reactivity with one, both or no mAbs did not result in any statistically significant differences (Mann-Whitney test: P > 0.05) between their median FHC concentrations. Since the absence of differences in their FHC levels was not attributable to a difference in the percentage distribution of HLA allotypes associated with high or low HLA-B/C FHC expression, our results indicate that FHC HLA A3 and/or A30 products detected in DDIA by these two mAbs only minimally contribute to FHC serum expression and that the assay is not limited by the failure to detect HLA-A FHC products in A3- and/or A30- individuals.