Tenascin in salivary gland tumours.

The distribution of tenascin immunoreactivity was analysed in salivary gland tissue and in various benign and malignant tumours of the salivary gland. In the non-neoplastic tissue, tenascin was seen in the areas of basement membranes of the ductal epithelium. No immunoreactivity could be observed in the serous or mucous glands. In pleomorphic adenomas, tenascin immunoreactivity could be seen in the stromal compartment. It was more pronounced in the dense stromal areas and chondroid elements than in the myxoid area. In Warthin's tumours, strong tenascin immunoreactivity could be observed in the basement membrane zone of the epithelial component. In the lymphatic component, faint reticular staining could be seen. In adenoid cystic carcinomas, acinic cell tumours and mucoepidermoid carcinomas, tenascin showed a linear stromal distribution. No intracytoplasmic immunoreactivity could be seen in any of the cases. The widespread tenascin positivity in salivary gland tumours suggests that tenascin may play a role in the induction and progression of salivary gland tumours, presumably by interfering with the normal parenchymal-mesenchymal interaction.


Small cell carcinoma of the ovary: an immunohistochemical and ultrastructural study with a review of the literature.

This is an immunohistochemical and ultrastructural study of two small cell carcinomas of the ovary with a review of the literature. These cases showed a dimorphic population of small and large cells sharply demarcated from each other. Cytokeratin 18 and vimentin were mainly expressed in the large tumour cells, some of which also stained for alpha-smooth muscle actin. Periodic-acid-Schiff-positive, alpha-1-antitrypsin-positive hyaline globules were present in one case. Ultrastructural findings included filamentous nucleolonema as well as evidence of smooth muscle differentiation. Some of these observations have not been previously reported. Certain of the above features seem to support a germ cell origin of small cell carcinoma, but they cannot be considered specific for germ cell neoplasms. Thus, small cell carcinoma of the ovary cannot be classified into one of the known categories of ovarian tumours at the present time.


Nodular sclerosing Hodgkin's disease and large cell lymphoma. Immunophenotypic characterization of a composite case.

Composite lymphomas have rarely been reported in Hodgkin's disease (HD), except in the lymphocyte predominance sub-type, and immunohistochemical investigations have been performed in only few cases. We describe the histological and immunophenotypical findings in a case of composite nodular sclerosing HD and high-grade, large cell non-Hodgkin's lymphoma (NHL). In our case HD and NHL cells displayed striking morphological and immunophenotypical divergence, suggesting a lack of correlation between the two neoplasms.


Venular endothelium binding molecules CD44 and LECAM-1 in normal and malignant B-cell populations. A comparative study.

Lymphocytes leave the blood via post-capillary venules by binding initially to their specialized endothelium. CD44 is a 80-90 kDa hyaluronate-binding glycoprotein involved in binding to endothelium of high endothelial venules (HEV). LECAM-1 is a 75-85 kDa glycoprotein with lectin activity interacting with human peripheral lymph node vascular addressin (PNAd) on HEV. This immunohistochemical study shows that CD44 and LECAM-1 are essentially coordinately expressed on B-lymphocytes. The mode and level of CD44/LECAM-1 expression dissect the peripheral B-cell development into stages that are closely linked to morphologically defined B-cell compartments. Although statistically correlated in B-cell leukaemias (p < 0.0009) and extranodal B-cell lymphomas (p < 0.003), expression of both molecules was less stringently coordinated in 127 B-cell neoplasms examined. B-cell chronic lymphocytic leukaemia, hairy cell leukaemia and mantle zone lymphoma were CD44/LECAM-1 positive, thus corresponding to their reactive counterparts. Correspondingly, follicular centre cell-derived lymphomas were devoid of both markers. Conversely, CD44 and LEC-AM-1 were infrequently detectable in extranodal malignant B-cell neoplasms, irrespective of their maturational state. Presence versus absence of CD44 and LECAM-1, alone or together, determined neither the leukaemic versus aleukaemic state nor the nodal versus extranodal tumour-forming phenotype of a B-cell tumour.


An immunohistochemical study of the breast using antibodies to basal and luminal keratins, alpha-smooth muscle actin, vimentin, collagen IV and laminin. Part I: Normal breast and benign proliferative lesions.

The distribution of simple epithelial (K8/18/19) and basal (myoepithelial) (K5/14) keratins, alpha-smooth-muscle actin, vimentin, collagen IV and laminin in normal mammary glands and in benign proliferative lesions was studied using monoclonal antibodies (mAbs). These antibodies (Abs) identified myoepithelial cells and luminal cells specifically. In lesions with adenosis and papillomas, the two-layered formation resembled that of normal glands with a purely myoepithelial-epithelial differentiation. In scleradenotic lesions, the main cell was of myoepithelial immunophenotype with intermixed trabecular-tubular proliferations of simple-type epithelium. The sclerosis seems to be the result of an irregular basal lamina synthesis by the myoepithelial cells. In contrast to these lesions, epitheliosis represents a purely intraluminal cell proliferation of clearly simple epithelial immunophenotype and of cells with a basal keratin phenotype, lacking myoepithelial differentiation antigen actin. The basal keratin type epithelium may represent post-stem or intermediate cells developing into luminal epithelium. Epitheliosis appears to be a purely epithelial hyperplasia with striking similarity to the regeneration of normal breast epithelium. The different proliferative patterns may give an explanation for differences in potential cancer risks of patients with these lesions.


An immunohistochemical study of the breast using antibodies to basal and luminal keratins, alpha-smooth muscle actin, vimentin, collagen IV and laminin. Part II: Epitheliosis and ductal carcinoma in situ.

A detailed immunohistochemical study has been carried out on 63 breast lesions with epitheliosis, ductal carcinoma in situ and clinging carcinoma (lobular cancerization), using antibodies directed against keratins 5/14 and 14, 15, 16, 18, 19, vimentin, smooth muscle actin, collagen IV and laminin. The results have shown that epitheliosis on the one hand and ductal in situ and clinging carcinoma on the other are immunohistochemically different epithelial lesions. Epitheliosis appears to be epithelial hyperplasia with keratin 5/14 and keratin 14, 15, 16, 18, 19-positive cells. Compared to epitheliotic cells tumor cells of clinging carcinoma, lobular cancerization and ductal carcinoma in situ expressed only luminal keratins 14, 15, 16, 18, 19 in 85% of the cases studied; whereas in 15% there was a basal keratin expression. From our results we conclude that the clinging carcinoma (lobular cancerization) represents the initial morphological step in the development of ductal carcinoma in situ and thus may be interpreted as a minimal ductal neoplasia. With the immunohistochemical demonstration of basal and luminal keratins it may be possible in individual cases to differentiate between benign and malignant in situ lesions of the breast.


Interferon induction of chicken MHC class I gene expression: phylogenetic conservation of the interferon-responsive element.

The 5' upstream region of a chicken MHC class I gene BF-IV contains sequence motifs similar to the interferon consensus sequences (ICS) contained in promoters of many mammalian interferon-regulated genes. To study a possible functional role of this putative chicken ICS, an oligonucleotide spanning the upstream sequences of the BF-IV gene (-174/-194) was cloned singly or in multiple copies before the herpes TK promoter controlling the chloramphenicol acetyl transferase (CAT) gene (pBLCAT2). Transient expression studies performed with primary chicken fibroblasts (CEF) showed that the chicken ICS represses constitutive promoter activity. The chicken ICS, however, enhanced CAT activity up to 20-fold following treatment with chicken interferon (IFN). Deletion analysis of the BF-IV promoter also confirms that the upstream DNA sequences (-174/-194) contain a functional ICS recognized by chicken interferon. The murine ICS of the H2-Ld gene was also activated by chicken interferon when introduced into CEF. IFN activation of chicken ICS containing reporters was also observed in transformed chicken fibroblast lines. We show that the chicken ICS binds two specific nuclear factors present in chicken fibroblasts which are induced by interferon. These factors were also capable of recognizing the mouse ICS, suggesting the conservation of a relevant DNA-binding protein. Taken together, these data indicate that the chicken ICS motif contained in a sequence from -174 to -194 of the BF-IV gene acts as a strong interferon-response element, which has been functionally conserved during about 270 million years of separate evolution of mammals and birds.


Chondroblastoma of bone. A clinical, radiological, light and immunohistochemical study.

The clinical and morphological findings of 53 chondroblastomas in the files of the Bone Tumour Registry of Westphalia are presented. The mean age of all patients was 19.2 years. The male-to-female ratio was 1.5:1. Forty-two of the tumours (79.8%) were located in the long tubular bones and short tubular bones of the hands and were closely related to the growth plate. Six cases (11.3%) were found in the flat bones, 4 cases (7.5%) in the tarsal bones and 1 case (1.9%) in the craniofacial bones. The characteristic radiological feature of 44 investigated lesions was a mostly eccentric radiolucency with a geographic pattern of bone destruction and matrix calcifications. Periosteal reaction was evident in 9% of the cases. Most tumours demonstrate the typical morphological features of chondroblastoma, but 3 cases resembled a giant cell tumour. In 2 cases a haemangiopericytoma-like growth pattern was observed. Nine of the tumours had an aneurysmal bone cyst-like component. Vascular invasion was seen in 1 case. Immunohistochemically most cells in 30 of the cases and fetal chondroblasts in 3 cases were strongly positive with vimentin and S-100 protein. Collagen type II was positive in the chondroid matrix of the tumours and in fetal cartilage tissue; collagen type VI was present focally around individual tumour cells and was always seen in the chondroid matrix of the lesions and in fetal cartilage. These findings support the cartilaginous nature of these tumours. In paraffin sections, 46.6% of the cases revealed a distinct positive reaction of some tumour cells with the monoclonal cytokeratin antibody KL1 (molecular weight 55-57 kDa). Only 4 of them demonstrated a coexpression with the other monoclonal cytokeratin antibody CK (clone MNF 116, molecular weight 45-56.5 kDa). In paraffin sections all fetal chondroblasts were negative with both cytokeratin antibodies. Frozen sections of 3 tumours showed a strong positive reaction with both cytokeratin antibodies in many chondroblasts, indicating an "aberrant" cytokeratin expression. Osteoclast-like giant cells stained positive with leucocyte-common antigen (LCA) and with the macrophage-associated antibody KP1, but were negative with the other macrophage-associated antibody MAC 387. Recurrence rate was 10.7%. The clinical course of all tumours was benign.


Production and characterization of monoclonal antibodies to porcine group C rotaviruses cross-reactive with group A rotaviruses.

Five monoclonal antibodies (MAbs) to porcine group (gp) C rotaviruses (Cowden and Ah strains) reactive with both gp A and C rotaviruses in cell culture immunofluorescence (CCIF) tests were produced and characterized. These MAbs reacted with three strains of gp A and two strains of gp C rotaviruses in a CCIF test and were classified into two groups based on their CCIF titers. The MAbs also reacted to various degrees with cell-culture-propagated porcine gp C rotavirus (Cowden) and bovine gp A rotavirus (NCDV) in an enzyme-linked immunosorbent assay by using the MAbs as capture antibodies. Fecal samples containing human, bovine, and porcine strains of gp A and C rotaviruses were positive when tested using one of the MAbs in this assay. The MAbs recognized VP6 of gp A rotavirus and the VP6 counterpart (41-kDa protein) of gp C rotavirus in a Western blot assay. Results of competitive binding assays on four MAbs indicated that gp A and gp C rotaviruses share three overlapping epitopes within a single antigenic domain. These results suggest that gp A and C rotaviruses share a common antigen located on the VP6 protein, which is recognized by certain MAbs in various serologic assays.


Analysis of epitopes on potato leafroll virus capsid protein.

Pepscan hexapeptides prepared to the capsid protein amino acid sequence of potato leafroll luteovirus (PLRV) were tested against both polyclonal and monoclonal antibodies. Twelve continuous epitopes were identified: 11 were detected by two different PLRV polyclonal antisera, but only 4 were detected by both antisera. The 12th epitope reacted with monoclonal antibody BG3. The location of most of the epitopes did not correlate well with antigenic areas predicted by computer algorithms. Comparison of the amino acid sequences of PLRV and southern bean mosaic virus capsid proteins allowed a preliminary assignment of epitopes 4-12 to different regions of the putative S domain of the PLRV subunit. Five out of 14 monoclonal antibodies and both of the polyclonal antisera reacted with epitope 1 at the N-terminus. ELISA data indicated that even though the N-terminus is hydrophobic, it is exposed at the surface of the particles.


Human oocytes express murine retroviral equivalents.

Unfertilized human oocytes expressed a gp70-related epitope as observed when staining section immunocytochemically with a panel of monoclonal antibodies against gp70 of murine leukemia virus. Some oocytes also expressed virus-like particles at the cell membrane. Follicular fluids, corresponding to these oocytes, contained p30- and gp70-related antigens, reverse transcriptase, and an increased titer of interferon. The three- to four-cell human cleavage stages did not contain the gp70-related epitope. It is concluded that human oocytes, but not early cleavage stages, express products that suggest the presence of an active endogenous retrovirus genome.


Detailed diagnoses and procedures, national hospital discharge survey, 1990.

This report presents statistics on conditions diagnosed and surgical and nonsurgical procedures performed in non-federal short-stay hospitals. The statistics are based on data collected through the National Hospital Discharge Survey from a national sample of the hospital records of discharged inpatients. Estimates of first-listed diagnoses, all-listed diagnoses, days of care for first-listed diagnoses, and all-listed procedures are shown by sex and age of patient and geographic region of hospital.


Second-generation anti-HCV tests predict infectivity.

Twenty-four blood donors found positive for the first-generation hepatitis C antibody (anti-HCV) test (Ortho EIA-I) and 88 of their recipients over the period from 1972 to 1990 were retrospectively investigated with different first- and second-generation anti-HCV tests. The aim of the study was to identify the infective donors and to evaluate the tests. Seven donors, who probably were infective carriers of HCV, were also second-generation test (EIA-II) positive, compared to only 3 out of 17 noninfective donors. Among the infected recipients, 14 out of 29 (48%) were positive for the second-generation test only. The second-generation test identified the infective donors in our study and was more sensitive than the first-generation test. We therefore recommend that blood donors are screened with EIA-II. Positive test results should be confirmed by the recombinant immunoblot assay (RIBA-II), and persons with positive or not conclusive RIBA-II should not be accepted as blood donors.


[The hemodynamic disorders in Sudeck's atrophy and the effect on them of interference therapy].

Interferential currents applied to the forearm fracture region of 80 patients with Sudeck atrophy eliminated hemodynamic changes in the affected limb as shown by capillaroscopy, rheovasography. The effect of the treatment is attributed to recovery of normal blood flow and microcirculation in the region of bone atrophy as well as analgetic action of pulse current.


[Antifibrosis effect of modified forms of catalase and superoxide dismutase in experimental silicosis].

The forms of catalase modified by treatment with dextran aldehyde were obtained and studied. Efficacy of the preparations containing native and modified forms of catalase and superoxide dismutase as well as their covalent bienzyme conjugate containing catalase-dextran aldehyde-superoxide dismutase was studied in rats with simulated silicosis. The preparations were administered into rats by means of inhalation and intraperitoneal injection. Positive protective effect exhibited a mixture of native enzymes and their covalent conjugate. The most pronounced additional effect was caused by the mixture of native catalase and superoxide dismutase as compared with modified preparation of superoxide dismutase. The preparation of bienzyme containing conjugate was less effective.


Surgical and non-surgical treatment of cancer of the oesophagus and the oesophagogastric junction: results of 200 consecutive cases.

200 consecutive, unselected patients with cancer of the oesophagus or the oesophagogastric junction (89 squamous, 110 adenocarcinoma or undifferentiated, 1 oat cell) between 1984 and 1987 were reviewed. Resection with postoperative adjuvant irradiation in the cases of squamous cell cancer, was carried out in 51 patients and non-surgical treatment [57 combined dilation and Nd-YAG-laser, 64 iridium 192 high-dose rate brachytherapy with or without 60 Gy external beam irradiation (EBR); 28 endoprostheses] was performed in the remaining 149 patients. The overall 5 year-survival rate was 9.2% (resections: 17.9%, non-resected: 5.2%). Resected nodal negative T1 or T2 patients had the best prognosis (45.8% 5-year survival). The median survival following dilation and laser was 3.4 months for all T-stages. Endoprostheses yielded a median survival of 1.7 months. Intracavitary brachytherapy gave the best palliative result with 6.5 months median survival, whereby only T1 and T2 patients benefitted from additional EBR. Histological subtype, age, sex or tumour localization did not influence survival. Multivariate analysis showed that in M0 patients the choice of treatment had a significant impact on prognosis.


[The characteristics of human immunodeficiency virus strains isolated from HIV-infected persons on the territory of the USSR].

Fifty-seven HIV-1 strains were isolated from peripheral blood lymphocytes of 102 HIV-infected persons involved in epidemic outbreaks in different cities of the USSR. The effectiveness of isolation was 29.1% in asymptomatic infection, 51.7% in cases with generalized lymphadenopathy, and 82.6% in persons with severe clinical manifestations. Identification of the isolates by indirect immunofluorescence, ELISA, reverse transcriptase activity, Western blot, electron microscopy, and polymerase chain reaction showed them to belong to HIV-1 type. Reproduction of the isolates in cell cultures was accompanied by cytopathic effect and syncytium formation. The isolated strains can be divided into two groups: (1) the poorly growing isolates with low or negative RT and ELISA results and (2) the isolates with high infectivity, broad spectrum of cell tropism, and high levels of RT and ELISA. These data show the correlation of biological properties of HIV-1 strains isolated in the USSR with those of HIV strains previously isolated in Europe, USA, and Africa.


[Deoxyoligonucleotide probes that differentiate antigenic and pathogenetic variants of the tick-borne encephalitis virus].

Experiments on molecular hybridization were carried out using a panel of 11 deoxyoligonucleotide probes complementary to different parts of tick-borne encephalitis (TBE) virus, strain Sophyin, genome. Under study were the TBE virus strains differing by 3 criteria: (1) source of isolation (patients with acute and chronic TBE, Ixodes persulcatus and D. nuttalli ticks, small mammals); (2) serotype (eastern and Siberian Aina/1448), (3) virulence for Syrian hamsters. RNA of all the strains was hybridized with kDNA, 90% of strains with probe Sh5 complementary to protein E gene, nucleotide positions 1285-1311. The highest differentiating capacity was observed with probes P131 and Sh3 complementary to genes of proteins ns2b and M. These probes reacted with RNA of 100% of highly virulent strains of the eastern serotype and only with 20-30% of strains of the Aina/1448 serotype of lower virulence. A certain differentiating capacity was demonstrated by probes Sh2 and P10 complementary to genes of prm and C proteins: they hybridized with RNA of 80% of eastern serotype strains highly virulent for hamsters and with only 20% of Aina/1448 serotype strains of low virulence. The panel of probes used revealed no significant differences among strains in relation to their isolation source, with the exception of a strain isolated from D. nuttalli ticks which reacted only with kDNA and probe P2 complementary to nsI protein gene, but not with other probes. The TBE virus strains isolated from patients with chronic TBE were shown to represent a genetically heterogeneous group.


Hydroxyl radical-mediated conversion of morphine to morphinone.

1. The hydroxyl radical-mediated conversion of morphine to morphinone (MO) was examined as an alternative to the enzymic reaction. 2. Hydroxyl radicals were generated by autoxidation of ascorbate in the presence of iron and EDTA. This system oxidized morphine to MO which was identified by h.p.l.c. and t.l.c. The reaction was dependent on the concentration of added Fe2+ and required the addition of ascorbate when Fe3+ was used. 3. Catalase inhibited production of MO whereas superoxide dismutase (SOD) had no effect. Addition of a large amount of H2O2 to the system resulted in a significant decrease in production of MO. No MO production was initiated by H2O2 itself. The oxidation of morphine was inhibited by typical hydroxyl radical-scavenging agents. These results indicate that morphine undergoes oxidation to MO by hydroxyl radical.


[The immunogenic activity of the Lassa virus structural proteins].

The immunogenic properties of Lassa virus GP1, GP2, and NP polypeptides were studied in rabbits. Lassa virus NP polypeptide, in contrast to GP1 and GP2 polypeptides, was shown to induce the highest titres of antibodies determined by IFA and ELISA tests. Moreover, the antibody relative avidity experiment showed that the anti-NP antibodies has ELISA index of 0.63 whereas anti-GP1 and anti-GP2 antisera had those of 0.49 and 0.28, respectively.


[The effect of low and high molecular weight dextrans on selected serum lipid parameters. 2].

The effect of dextran infusions on plasma levels of total cholesterol, LDL and HDL cholesterol, apolipoprotein B and AI and triglycerides is investigated within a patient group. Some plasma lipids and lipoproteins still remain significantly lowered after the end of the 10 days treatment period. Comparing the normolipidaemic with the hyperlipidaemic patients of type IIa and IIb the degree of alterations is different between these 3 groups.


[Endoscopic-sonographic control of cystogastric catheter drainage of pancreatogenic fluid collections].

In 1985, Hancke published a report on cystogastrostomy using a double pigtail catheter as an alternative to surgical drainage of pseudocysts. Between 1986 and 1991, with the aim of testing the technique, we carried out a prospective study in 39 patients with 40 pancreatic collections of fluid. The object of the study was to identify those collections of fluid that would be suitable for cystogastric drainage. Among the first 20 patients thus treated, permanent evacuation of the cyst was achieved in eleven. In the other nine patients, the reasons for the failure of cystogastric drainage included to immature a cyst, too small a cyst, prior cyst infection and status after a BII resection. For the patients No. 21 to 40, these conditions were adopted as exclusion criteria, with the result that we were able to increase the percentage of permanent emptying to 75%. This makes cystogastric drainage a genuine alternative to surgical and other drainage procedures. As a minimally invasive intervention, it is a first choice therapeutic procedure in suitable pancreatic pseudocysts. If cystogastric drainage is shown not to be feasible, the possibility of employing percutaneous drainage should be investigated. Surgical drainage procedures are reserved for use in such cases as cannot be treated with catheter drainage.


Is it still worthwhile to treat bone metastases from differentiated thyroid carcinoma with radioactive iodine?

From 1964 to 1989, bone metastases were found in 28 of 600 patients operated on for differentiated thyroid carcinoma. Bone metastasis was the presenting symptom in 15 (54%) patients, was detected from the initial symptom in 4 (14.5%) patients, and occurred subsequently in 9 (32%) patients, with an average lag time of 4.5 years after surgical treatment. Pathological pattern of the thyroid cancer was follicular in 26 (93%) patients and papillary in 2 (7%) patients. Bone metastatic involvement was multiple in 21 (75%) patients and associated with other synchronous or metachronous distant metastases in 13 (46%) patients, especially in the lung (10 patients) or the brain (3 patients). The primary treatment of thyroid carcinoma was total thyroidectomy in all 28 patients, with additional modified neck dissection in 8 patients. All 15 patients presenting with symptoms had bone metastases demonstrated by x-ray studies. Six of the bone metastases only took up radioactive iodine 6 weeks after total thyroidectomy, as did 2 of 4 bone metastases detected at initial observation and 4 of 9 metachronous bone metastases. All 12 patients with functioning bone metastases were given radioactive iodine therapy; 4 of the metastases were surgically resected. Only 2 patients with bone metastases showed a complete response after an ablative dose of I-131; none of the metastases had been demonstrated by x-ray studies. Radioactive iodine therapy cures no more than 17% of patients with bone metastases taking up radioactive iodine and 7% of all patients with bone metastases. All patients cured of bone metastases were given radioactive iodine, either alone, or combined with other treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Invasion by cultured human follicular thyroid cancer correlates with increased beta 1 integrins and production of proteases.

A recognized model of tumor invasion requires cells to adhere to epithelial basement membrane and extracellular matrix components triggering release of proteases thus allowing cancer cells to invade the substrate. This adhesion is mediated by beta 1 integrins, a family of receptors to substrates such as collagen, laminin, and fibronectin. In order to study tumor invasion in follicular thyroid cancer (FTC), we used cell lines derived from a single patient's FTC primary tumor (FTC-133), neck lymph node metastases (FTC-236), and lung metastases (FTC-238). In vitro invasion as determined by the ability of the tumor cells to penetrate Matrigel was assessed by scanning electron microscopy. FTC-133 did not invade, FTC-236 was moderately invasive, and FTC-238 was highly invasive. Immunoprecipation with a monoclonal antibody to beta 1 integrin subunits and SDS-PAGE showed increased synthesis and flow cytometry showed increased expression of this subunit in FTC-236 and FTC-238 compared to FTC-133. Proteolytic activity was assessed by gelatin zymography. FTC-238 cell extract and conditioned media exhibited a more complex array of proteases consistent with activated type I collagenase and stromelysin compared to the less invasive clones, however 72 and 92 kd gelatinases consistent with type IV collagenases were present in the conditioned media from all three lines. In conclusion, in vitro invasion parallels in vivo metastasis by the source cells in the FTC-133/236/238 cell-lines. The ability to invade basement membrane preparation correlates with increased synthesis and expression of beta 1 integrins and activation of tumor proteases.


[Development of new enzyme inhibitors for the treatment of AIDS[ ].

Two different approaches can be used to discover new lead structures for further drug design. Till now, de novo drug design, however, has not led to compounds active against HIV. The more classical approach, based on screening programmes, has led to the discovery of three different enzyme inhibitors active against HIV: transition state analogues (protease inhibitors), antimetabolites (azidothymidine and analogues as reverse transcriptase inhibitors), and TIBO and its congeners (reversible reverse transcriptase inhibitors).


Postoperative hearing recovery in a case of delayed hearing loss after acoustic neurinoma removal.

Delayed postoperative hearing loss after acoustic neurinoma removal is seldom observed. The presented case illustrates the phenomenon of delayed postoperative hearing loss which was observed 4 days after removal of a large acoustic neurinoma. Intraoperative brainstem auditory evoked potentials (BAEP) revealed a gradual loss of wave V with preservation of wave I. In animal experiments a dissociated loss of BAEP has been associated with impairment of microcirculation due to secondary edema. Vasoactive treatment was initiated and after 11 days a partial hearing recovery could be documented. Transient disturbance in microcirculation of vasa nervorum of the cochlear nerve is assumed to be responsible for postoperative hearing fluctuation.


[A comparative study of the diagnostic value of polyclonal and monoclonal antibodies to human IgM in immunoenzyme diagnostic agents].

Monoclonal antibodies (McAb) to human IgM, capable of recognizing antigenic determinants of different character, have been obtained. Three type-specific McAb have been used in diagnostic systems for the determination of specific IgM antibodies in the sera of patients with hepatitides A and B. The affinity constant and high specificity of McAb have made it possible to change affinity-purified polyclonal antibodies to heavy chains of IgM for the gamma fraction of hybridoma-induced ascitic fluids without decreasing the sensitivity and specificity of test systems. The main advantages of McAb are the standard character of the reagent and reproducibility of its properties.


[Diagnosis and therapy of geriatric aphasia patients following cerebrovascular stroke].

Aphasia is common in elderly patients with stroke. This paper presents some results of aphasia therapy within the activation phase (acute aphasia) and the syndrome-specific learning phase (until the 24th week of treatment). A phase-specific therapeutic concept was developed to connect stimulation and cirumvention method and compensatory techniques. The results attest to the success early after stroke regarding development of speech pathology logopedic diagnosis and therapy.


A prospective randomized study of two alternating, non cross-resistant chemotherapies for advanced Hodgkin's disease.

Fifty-four newly diagnosed patients with advanced Hodgkin's disease were randomized between two alternating non cross-resistant chemotherapies: MOPP-ABVD (MOPP: Mustine, Vincristine, Procarbazine, Prednisone-ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine) and MOPP-ABVD-CEM (CEM: Carmustine, Etoposide, methyl-GAG). There were no significant differences between the two therapies as far as complete remission, survival, relapse free survival and toxicity were concerned. This study does not support the use of MOPP-ABVD-CEM for improving the long-term outcome of patients with advanced Hodgkin's disease.


[The limits of saving the extremity--amputation versus resection].

On the basis of the extensive data contained in the Vienna Bone Tumor Register, i.e. 839 primary malignant bone tumors, as well as of 554 cases treated at the Orthopedic Department of the University of Vienna Medical School, a comparison between the methods of surgery applied at pelvis and extremities during the past two decades can be drawn. Resectional therapy had been performed in twice as much patients as amputation therapy, and barely 20%, mostly with multiple metastases, had been merely treated with palliative surgery or were just biopsied and underwent chemo- and radiotherapy. An analysis of amputations and resections, subdivided into pelvis and sacrum resections, resectional reconstructions and resectional reimplantations at the extremities, shows approximately the same low incidence of local recurrences in the groups amputation versus resection, but a significantly higher involvement of pelvis and sacrum resections as well as no local recurrences in the group of 48 resectional reimplantations. As regards the oncologic radicality of surgical margins, in cases of resections, as compared to amputations, about twice as much inadequate operations had to be accepted, though. The fact that the local recurrences did not increase to the same degree, but were approximately equilibrated, seems to be due to the new chemotherapeutic treatment which had been initiated at the same time as the frequent application of resectional therapy. The conservation of extremities contains twice as high a risk of inadequate operation, but it is, in cases of effective chemotherapy, comparable with the former results of amputations, as regards local recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)


Cell kinetics in skin disorders with disturbed keratinization.

A relatively simple immunohistochemical method was developed and used on cryostat sections. The monoclonal antibody Ki67 was used as marker for actively cycling cells and Pab601 for germinative cells. Counts were expressed as Ki67- or Pab601-positive cells/mm. In order to improve our understanding of the pathogenetic mechanisms in skin disorders with disturbed keratinization we have measured cell kinetic values in dyskeratosis follicularis, pemphigus benigna familiaris chronica, autosomal dominant ichthyosis vulgaris, X-linked recessive ichthyosis, atopic dermatitis and psoriasis and compared them with previous values derived with autoradiography using tritiated thymidine. The results showed that microscopical acanthosis is related to an increase of the germinative population, while the increased epidermal turnover is associated with increased numbers of cycling cells. The cell kinetic changes seem to be all secondary except in psoriasis where a dysregulation in the epidermal growth may cause the epidermal changes. This simple method allows quick evaluation of drug efficacy which might be useful in atopic dermatitis and psoriasis.


Aluminium hydroxide uptake in the stomach and in the intestine of the rat: a histochemical study.

Using the histochemical stains aluminon, solochrome azurine and solochrome cyanine, intracellular binding of aluminium was examined in the mucosa of the stomach, duodenum, jejunum and ileum of adult rats. A first group of rats (n = 42) was sacrificed 1, 3, 6, 12, 24, 48 and 96 h after a single (300 mg x kg-1) oral administration of aluminium hydroxide. A second group of animals (n = 30) received daily the same dose of Al(OH)3 and was euthanatized after 3, 4, 5, 6 and 7 days of treatment. Aluminium deposits occurred only in the antral glands of the stomach and in rats treated for at least 3 days. The reactive deposits are located in the cytoplasm of the upper glandular cells and in the lumen of the antral glands. These results suggest that aluminium is absorbed through the antral mucosa and may be re-excreted through the glandular mucus flow into the digestive lumen where it will be absorbed again. We hypothesize that the metal could act as a delayed-effect drug.


[Role of liver transplantation in the treatment of metastatic disease of the liver].

The authors report their experience of liver transplantation for metastatic tumor in 6 patients. Although good palliation can be offered with prolonged survival in some patients, secondaries of the liver remain the poorest indication for liver transplantation. A prospective multicentric study would be needed to evaluate the usefulness of post-transplantation chemotherapy.


CSF neurotransmitter metabolites and short-term outcome of patients in coma after head injury.

The main metabolites of the neurotransmitters noradrenaline, dopamine, and serotonin, methoxy-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) respectively, were estimated by HPLC with electrochemical detection in CSF samples from 24 patients in coma after head injury, 1 to 12 (mean 3.0) days from accident, and from 24 age- and sex-matched subjects undergoing myelography for possible herniated disk. Analysis of variance with age as covariate, revealed significantly elevated levels of all three metabolites in the patients group. The concentrations of 5HIAA were negatively correlated to the score in the Glasgow Coma Scale. Fourteen patients who recovered with no or minor neurological deficits, had significantly lower CSF 5HIAA levels compared to the ten patients who had a bad outcome (death), while there were no differences regarding HVA or MHPG concentrations. The possibility of a connection of the high neurotransmitter turnover during coma to the development of post-traumatic depression is discussed.


CSF galanin and neuropeptide Y immunoreactivity in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) has been associated with degenerative changes in cholinergic and dopaminergic neurons in several brain regions. Since acetylcholine is colocalized with the neuropeptide galanin in certain neuronal populations, we measured the concentration of this neuropeptide and neuropeptide Y in cerebrospinal fluid (CSF) of 11 patients with PSP and in 16 age-matched healthy controls. No significant alterations in the CSF levels of galanin or neuropeptide Y were found.


IgM M-protein in a patient with sensory-dominant neuropathy binds preferentially to polysialogangliosides.

A 77-year-old man presented sensory-dominant neuropathy associated with IgM M-protein reacting with various gangliosides. The M-protein bound to gangliosides with polysialosyl residue, such as GD1b, GD3, GT1b, GT3, GQ1b, and GQ1c. In addition, GD1a, GM3 and LM1, having a terminal monosialosyl epitope, were also recognized. Previously, Ilyas et al. described a similar case in which sensory symptoms were associated with IgM M-protein reacting with gangliosides containing a disialosyl group, such as GD3, GD1b, and GT1b, but not GM3 and GD1a. It is suggested that the reactivity of IgM M-protein with polysialogangliosides may be associated with the pathogenesis of sensory-dominant neuropathy.


CSF myelin basic protein, IgG and IgM levels in 101 MS patients before and after treatment with high-dose intravenous methylprednisolone.

A total of 101 patients (62 women; 39 men) with definite MS were treated with 1000 mg methylprednisolone (MP) intravenously for 10 consecutive days. Immediately before and after MP treatment clinical scoring (Kurtzke's Expanded Disability Status Scale) and CSF analysis were performed. Before MP treatment CSF MBP, IgG and IgM immunoglobulin levels (CSF Ig, index and intrathecal synthesis) were significantly elevated. The mean CSF MBP levels were significantly higher in the relapsing-remitting (RR) and chronic progressive MS patients with relapses (CP + RR) than in the CP group without a RR disease course, respectively 2.1, 2.3 and 1.5 micrograms/l. A weak positive correlation was found between CSF MBP level and EDSS in the RR MS group (r = 0.34). CSF MBP was significantly correlated with IgM index (r = 0.36), IgM synthesis (r = 0.26), but not with the IgG levels. Therefore demyelination seems to be related to intrathecal IgM production. After MP treatment mean (median) EDSS decreased from 4.4 (4.0) to 3.3 (3.0). Except for Q albumin and IgM index, all CSF immunoglobulin levels decreased significantly after MP. The mean CSF MBP returned to reference values. In the RR group the decrease in CSF MBP was significantly correlated with the change in EDSS (r = 0.39). CSF MBP seems to be a good parameter for disease activity in relapsing MS. Following treatment CSF MBP was found to be related with the change in IgM index (r = 0.30). MP treatment reduces CSF MBP and intrathecal IgM in a similar way indicating a relation between these 2 parameters.


Neuronal uridine metabolism.

Uridine and other nucleic acids form part of RNA, DNA, coenzymes, second messengers, etc. Uridine uptake in nerve cells is an expression of neuronal RNA synthesis. More knowledge of uridine functions in neurones may give a better understanding of mechanisms underlying dementia, and they could be useful in treating brain tumors. Pakkenberg and co-workers have studied the uridine uptake in the brains of mice and monkeys under various conditions (after hypoxia, after carbon-dioxide treatment, after MPTP treatment, after electrostimulation, etc.) and the results are correlated with other biological brain parameters.


Monoclonal antibodies with selective specificity for Alzheimer Tau are directed against phosphatase-sensitive epitopes.

A modified form of the microtubule-associated protein Tau is the major component of the paired helical filaments (PHF) found in Alzheimer's disease. The characterization of these posttranslational Tau modifications is hindered by the lack of sufficient PHF-Tau-specific markers. Here we describe several monoclonal antibodies, prepared by immunization with PHF, two of which showed a selective specificity for PHF-Tau without cross-reactivity with normal Tau. Epitope recognition by these two monoclonals was sensitive to alkaline phosphatase treatment. In Western blotting these monoclonal antibodies reacted specifically with the abnormally phosphorylated epitopes on Alzheimer's disease-associated PHF-Tau. One of the new antibodies can be used for the construction of a sandwich enzyme-linked immunosorbent assay for the specific detection of PHF-Tau without cross-reactivity to normal Tau proteins.


The fate of desmin and titin during the degeneration and regeneration of the soleus muscle of the rat.

We studied the fate of desmin and titin in rat skeletal muscle during a cycle of degeneration and regeneration induced in vivo by the inoculation of a snake venom. Cryosections of muscle were labelled using antibodies to the two proteins, and examined at fixed time points after venom injection. Early pathological changes in the muscle, such as hypercontraction, preceded the loss of desmin. Immunolabelling using anti-desmin antibodies showed that desmin bridges were still intact when adjacent myofibrils were no longer aligned. The results suggested that although the hydrolysis of desmin is not necessary for the hypercontraction of muscle fibres, it probably contributes to complete fibre breakdown. Titin, or at least the part which lies close to the M-line, remained intact longer than desmin, but was also hydrolysed prior to complete disintegration of the fibres. Both desmin and titin were re-expressed in the regenerating myotubes by 2 days after venom inoculation, and became well organised even before the myofibrils became aligned. We conclude that desmin and titin are involved in both establishing and maintaining the structural integrity of the muscle fibres.


Determination of the early age of onset of equine recurrent laryngeal neuropathy. 1. Muscle pathology.

The age of onset of equine recurrent laryngeal neuropathy has not been ascertained, although the clinical condition of left laryngeal hemiplegia ("roaring") has been recognized for centuries. The purpose of this study was to evaluate the laryngeal muscles of draft horse foals for the presence of fiber-type grouping, indicating denervation and reinnervation, and to determine if histological evidence of recurrent laryngeal neuropathy was present. Abductor and adductor laryngeal muscles from the left and right sides were collected immediately after euthanasia from male draft horse foals, six less than 2 weeks and four 6 months of age, and stained for myosin ATPase. A morphometric test was used to objectively evaluate several areas from each muscle for fiber-type grouping. Extensive fiber-type grouping which was characteristic of recurrent laryngeal neuropathy was found in one of the young foals and all of the older foals. Four of the young foals had some areas of fiber-type grouping suggestive of mild, early changes associated with recurrent laryngeal neuropathy. One of the young foals had no fiber-type grouping present in any of the laryngeal muscles evaluated. These findings suggest an early age of onset of recurrent laryngeal neuropathy.


Alexander's disease in infancy and childhood: a report of two cases.

Two cases of Alexander's disease are described. One case of infantile onset died at the age of 6 months and the second case was of the juvenile type with onset at 2 years and death at 10 years. A clinical diagnosis of this disease is difficult since signs can vary according to the age of the patient. The severity of the pathological changes can also depend upon the age of onset of this disease, but they are restricted to the central nervous system. The Rosenthal fibre is the characteristic feature of Alexander's disease and we have examined for the first time its ultrastructure and immunocytochemical characteristics at the electron microscopical level and demonstrated coexpression of anti-glial fibrillary acidic protein and anti-ubiquitin antisera.


Secretory meningioma associated with numerous meningothelial rosettes.

A case of secretory meningioma with numerous meningothelial rosettes is reported. A 66-year-old man with moyamoya disease gradually developed skull deformity, and underwent surgery for the skull tumor overlying the hemisphere. Histological examination disclosed numerous meningothelial rosettes quite similar to those induced by subarachnoid injection of epinephrine and pseudopsammoma bodies described by Kepes. This may be the first case of meningioma associated with numerous rosette formations.


Pseudomembranous and membranous conjunctivitis. Immunohistochemical features.

A 63-year-old man, who had for one month been on sulfasalazine therapy, developed general malaise, high fever, severe stomatitis, and bilateral necrotizing pseudomembranous conjunctivitis with corneal erosion, identical to that seen in the Stevens-Johnson syndrome. Topical therapy with antibiotics and aprotinin rapidly healed the corneal surfaces, while densely adherent true membranes developed on the conjunctiva, and were removed surgically several times during the next week. After the acute stage, subtle subepithelial conjunctival scarring, superficial punctate keratitis, dry eye syndrome and fluctuating irregular corneal astigmatism became evident, but good visual acuity, lid function and ocular motility were retained. Histopathologic study of conjunctival membranes from two cases of membranous conjunctivitis revealed polymorphonuclear leukocytes within a matrix composed of fibrin, tenascin and fibronectin. In older membranes, histiocytes were additionally found. Surgical debridement of such membranes removes a substratum of inflammatory debris that is likely to promote secondary infection, fibrosis and symblepharon formation, and may decrease rather than increase subsequent scarring of the necrotized conjunctiva.


An immunohistochemical and ultrastructural study of case of small-cell neuroendocrine carcinoma in the ampullary region of the duodenum.

One case of small-cell neuroendocrine carcinoma in the ampullary region of the duodenum is reported. The histological appearance of the tumor was identical to pulmonary small-cell carcinoma. Neuroendocrine differentiation was demonstrated immunohistochemically by positive immunoreaction for neuron specific enolase, Leu-7 and chromogranin, and ultrastructurally by the presence of scanty dense-core neurosecretory type granules. Small-cell neuroendocrine carcinoma in the ampulla of Vater is extremely rare. To our knowledge, this is the sixth reported case.


Ontogeny of glycerol phosphate dehydrogenase-positive oligodendrocytes in rat brain. Impaired differentiation of oligodendrocytes in the myelin deficient mutant rat.

The ontogeny of oligodendrocytes in the myelin deficient (md) rat mutant and in control rats was explored immunohistochemically using an antiserum against the oligodendrocyte specific enzyme, glycerol phosphate dehydrogenase (GPDH), and the avidin-biotin complex technique. In control rats, GPDH was demonstrated to be expressed relatively early in oligodendrocyte differentiation, prior to either myelin basic protein or proteolipid protein expression. With development, oligodendrocytes containing GPDH increased in number, apparent staining intensity, cell soma area and process elaboration. Fewer GPDH+oligodendrocytes were observed in the brain of mutant rats than in unaffected littermates at all developmental ages, and major developmental increases in oligodendrocyte density were delayed. The density of GPDH+oligodendrocytes was reduced by about 40% in both the corpus callosum and in the cingulate cortex of P22-25 and mutants compared with control rats. The oligodendrocyte cell soma area was not influenced by the md condition, and increased 2-fold with development in rats of both genotypes. The area of coronal sections occupied by the corpus callosum increased about 2.5-fold with development, and was 30% smaller in mutant rats late in their lifespan than in unaffected littermates. The reductions in oligodendrocyte density reported here are of insufficient magnitude to fully account for biochemically measured reductions in oligodendrocyte gene expression accompanying the md trait, indicating that gene expression per oligodendrocyte is also impaired. Cell counts in control rats also revealed that oligodendrocytes are overproduced during development. Cell density and the total number of corpus callosum GPDH+oligodendrocytes per section were maximal at P22-25 and then decreased to adult values. These results suggest that glial cells, like neurons, may be generated in excessive numbers, and some subsequently die, as a normal concomitant of development.


Effect of seizure activity and calpain inhibitor I on LTP in juvenile hippocampal slices.

Kainic acid-induced seizure activity in adult rats produces an impairment of long-term potentiation induction in hippocampal slices. As the consequences of seizure activity are different in adult and juvenile rats, we tested the ability of hippocampal slices prepared from kainate-treated juvenile rats to exhibit long-term potentiation. Long-term potentiation was induced by theta-burst stimulation and was not significantly different in slices prepared from control or kainate-injected juvenile rats (16-18 postnatal days). Short-term potentiation, however, was reduced in the kainate-treated juveniles. Calpain inhibitor I has been shown to prevent long-term potentiation formation in adult hippocampal slices, and we evaluated its effect on long-term potentiation in hippocampal slices from juvenile rats. Calpain inhibitor I produced a significant reduction in the degree of long-term potentiation induced by theta-burst stimulation in hippocampal slices prepared from 14-20 postnatal day-old animals. The results are consistent with the notion that, although similar mechanisms participate in the formation of long-term potentiation in juvenile and adult animals, juvenile animals are much more resistant than adult animals to the consequences of seizure activity.


Neuroendocrine regulation of cyclic AMP formation in osteoblastic cell lines (UMR-106-01, ROS 17/2.8, MC3T3-E1, and Saos-2) and primary bone cells.

The effect of four different neuropeptides and norepinephrine (NE) on cyclic AMP formation in four different osteoblastic cell lines and in isolated neonatal mouse calvarial bone cells has been examined. In the rat osteosarcoma cell line UMR-106-01, vasoactive intestinal polypeptide (VIP, 0.001-1 microM), calcitonin gene-related peptide (CGRP, 0.3-30 nM), and NE (0.1-300 microM), but not neuropeptide Y (NPY, 0.001-1 microM) or substance P (SP, 0.1-10 microM), caused a dose-dependent stimulation of cyclic AMP formation. The stimulatory effects were synergistically potentiated by forskolin (0.1-3 microM). The effects of NE and VIP were time dependent, with an optimal effect seen at 5 minutes. The amount of cyclic AMP accumulated in cells stimulated with NE and VIP was in the same range. The amplitude of the cyclic AMP response induced by CGRP was smaller than that caused by VIP and NE. In the human osteosarcoma cell line Saos-2, NE (0.1 microM) and VIP (0.3 microM) stimulated cyclic AMP formation, and the effect was synergistically potentiated by forskolin. In the absence of forskolin, no effect of CGRP (30 nM) could be seen in the Saos-2 cells, but in the presence of forskolin (3 microM) a stimulatory effect was observed. SP and NPY did not change basal cyclic AMP levels in Saos-2 cells. In the osteoblastic osteosarcoma cell line of rat, ROS 17/2.8, NE (0.1 microM) caused a significant stimulatory action on cyclic AMP formation that was synergistically potentiated by forskolin (3 microM), VIP, CGRP, and SP did not affect the cellular content of cyclic AMP in ROS 17/2.8.(ABSTRACT TRUNCATED AT 250 WORDS)


Speech--a key function of man. Reflexions of a neurosurgeon.

Man is distinguished and differentiated from other living creatures by possessing less genetically determined characteristics, behaviour and reactions, with fewer features fitting him for a special environment. For this reason he enjoys greater freedom and adaptability. In order to be able to pass on the necessary lessons for survival, man must have command of his speech, and as a species can only exist within communities. This presupposes an instinctive drive to make rules and regulations for ordered living in society. Speech is not only a means of communication but also the basis and precondition of abstract thinking. Complete aphasia implies the loss of this ability. It would deprive man from the most important of his key functions. Therefore it is inhuman. These reflections have convinced me absolutely, that neurosurgical interventions, which would have the predictable result of total aphasia, must not be performed, even though prolongation of life, but without speech, might thus be bought.


Antigen specific suppressor T cells respond to cytokines released by T cells.

These studies were conducted to examine the cytokine requirement for clonal expansion of regulatory T cells. It was observed that the in vivo administration of recombinant IL2 (rIL2), rIL5 or interferon (IFN) gamma at the time of immunization with pneumococcal polysaccharide Type III (SSS-III) resulted in substantial suppression of the antibody response in each case. Using our well established cell transfer system we found that such suppression of the antibody response could be transferred using 10-100-fold fewer primed spleen cells providing these cells were treated in vitro with rIL2 before cell transfer; spleen cells from unimmunized mice or from mice primed with an unrelated antigen and then treated with rIL2 did not cause suppression of the antibody response to SSS-III, thereby eliminating the possibility of non-specific carry-over effects induced by rIL2. We also found that the in vivo administration of anti-IL2 receptor antibody inhibited the generation of Ts cells in vivo. Spleen cells from SSS-III primed animals treated with rIL4, rIL5 and IFN gamma--but not rIL6--likewise are able to transfer suppression of the antibody response with fewer cells than that required using primed cells not treated with cytokines. Thus, these studies indicate that Ts cell activity is greatly influenced by cytokines. The studies also suggest that these cytokines may be required during the activation and/or clonal expansion of Ts cells.


Biologic response modifiers as antivirals in immunosuppressed hosts.

A wide variety of immunomodulators/biologic response modifiers (BRM) have been demonstrated to provide broad spectrum antiviral activity against both RNA and DNA viruses in several animal species. Dramatic decreases in mortality, reduced virus titers in tissues, and reduced histopathology can be produced. The antivirally effective agents include microbially derived materials, polyanions, cytokines, and chemically diverse small molecular weight chemicals. Antiviral efficacy with BRM treatment has been shown in numerous kinds of immunosuppression, emphasizing the potential for BRM treatment in immunocompromised patients. The greatest protective effects are observed with prophylactic or early therapeutic treatment. BRMs act indirectly, most likely by activating cells and/or inducing antiviral mediators early in the course of viral pathogenesis. In general, viral specific immune responses in BRM-treated and infected mice are absent or similar to those in untreated mice. Because BRMs are pleiotropic in their immunomodulatory effects, it has been difficult to establish whether one cell type or mediator is critical for the broad spectrum antiviral activity. Interferon appears to be critical for some small molecular weight synthetic compounds, but does not appear to explain all the antiviral activity of certain large molecular weight polyanions. Whether there is a unified antiviral mechanism among different BRMs remains to be determined.


[The gamma nail. A new implant for the management of hip para-articular fractures].

An alternative treatment of fractures of the coxal femur side is a new implant called "GAMMA-NAIL". The article describes the new implant and the operative technique. Furthermore, we present the results of a first series of 58 patients, mainly women (w:m = 8:1) with an average on age of 78.09 years. Although these patients were characterised by a number of complicating factors, it was possible to mobilise 86.2% at an average of 9.4 days after surgery with full load. We present a report on the quality of walking, a pain report, data on the mobility of joints and the x-ray findings. The 5.1% of infections and 8.6% of operative and postoperative complications we have to face, are described in detail.


Characterisation of passively transferred antigen arthritis induced by methylated bovine serum albumin in the rat: effect of FK 506 on arthritis development.

The conditions necessary for the passive transfer of antigen arthritis induced by methylated bovine serum albumin (mBSA) in the rat have been studied. Spleen cells from immunised rats were not capable of transferring disease unless they were first activated in culture with mBSA or concanavalin A. Cells from sham-immunised animals could not be activated to transfer the arthritis. The immunosuppressant drug FK 506 could inhibit the development of the arthritis when present during the activation period in culture or when dosed to the recipients of activated cells.


Simultaneous fluorometric determination of intracellular polyamines separated by reversed-phase high-performance liquid chromatography.

A reversed-phase HPLC technique in combination with fluorescent detection is described for simultaneous quantification of the precolumn Dansyl derivatives of intracellular amines. The derivatives were stable for at least one week, kept protected from the light at -20 degrees C. The detection limit was between 1 and 5 pmol for all tested polyamines. Serotonin coeluted with tryptamine. The method has a very good reproducibility for both, retention times and chromatographic peak areas. The average recovery of standard amine solutions added to cellular extracts was estimated to be higher than 90%. The described method enables a rapid, reliable and reproducible quantification of biogenic and related polyamines in biological fluids and tissues.


Behaviour of several 'progression markers' during the HIV-Ab seroconversion period. Comparison with later stages.

Two acute phase reactants, four cytokines, five soluble factors and lymphocyte subpopulations have been simultaneously evaluated in 16 subjects before and closely after the HIV-Ab seroconversion time. The same variables have also been determined in 50 HIV-Ab-negative high risk subjects, in 36 CDC II-III and in 30 CDC IV patients, utilizing a mixed longitudinal epidemiological model. The results show significant variations of few parameters in the early phases (increase: sCD8, beta-2-Microglobulin, sIL-2R, sCD23, Neopterin, IFN-alpha; decrease: CD4+ lymphocytes). In the course of the disease, many others parameters progressively increase (IFN-tau, IL-4, IL-6, acid-alpha 1-glycoprotein, alpha 1-antitrypsin) or decrease (B- and T-lymphocytes). Ferritin, in particular, highly increases only in CDC IV stage. These data may be useful to monitor patients during the entire course of their disease and to suggest the time elapsed from seroconversion.


Modulation of neurally mediated airway microvascular leakage in guinea-pig airways by beta 2-adrenoceptor agonists.

The effect of two beta 2-adrenoceptor agonists, salbutamol (100 micrograms/kg i.v.) and broxaterol (100 micrograms/kg i.v.), on airway microvascular leakage induced by vagal stimulation was studied in anaesthetised guinea pigs. Airway microvascular leakage was measured by Evans blue extravasation. Broxaterol, but not salbutamol, inhibited Evans blue dye extravasation at all airway levels, an effect prevented by pretreatment with propranolol (1 mg/kg). Neither of the beta 2-agonists had any effect on substance P-induced Evans blue dye extravasation. Broxaterol inhibits the prejunctional release of tachykinins from airway sensory nerves by stimulation of beta-receptors. The mechanism by which beta-adrenoceptor agonists prevent airway microvascular leakage deserves further study.


Dexamethasone induces a down regulation of rat mast cell protease II content in rat basophilic leukaemia cells.

Corticosteroids are widely used to treat severe allergic and inflammatory disease in which mast cells have been implicated as playing an important role. It has been previously shown that in vivo treatment with large bolus doses of corticosteroid can induce a down regulation of the number of IMMC in the rat. Previous in vitro studies of the RBL cell line have shown that culture in the presence of high doses of dexamethasone can induce an increase in cellular histamine content similar to that induced by other agents known to reduce the rate of cell division such as 5-hydroxyurea or sodium butyrate. In our studies the rat mucosal mast cell like cell line RBL-2H3 was cultured in the continuous presence of dexamethasone for periods of up to 4 weeks. Cell-associated histamine levels were found not to increase significantly at the doses of the corticosteroid we used. Of greater interest was the observation that levels of the mucosal mast cell specific protease RMCPII were dramatically reduced in these dexamethasone-treated cultures even at doses that might be considered to be physiologically relevant. This effect could be observed at 3 days after dexamethasone treatment and a continued reduction of RMCPII content was noted up to 4 weeks, at which time RMCPII levels were less than 5% of the control values in 10(-7) M dexamethasone treated cells. 5-Hydroxyurea did not reduce cellular RMCPII content even at a concentration which substantially reduced the rate of cell division and significantly increased cell associated histamine content.(ABSTRACT TRUNCATED AT 250 WORDS)


Changes in corticosterone levels under different degrees of acute inflammation in mice.

Carrageenan of different concentrations was injected into the 6-day-old air pouch in mice. It was found that 12 mg carrageenan caused a significant increase of plasma and exudate corticosterone levels at 24 h, while 1 and 3 mg carrageenan could only induce a significant increase of exudate corticosterone at 4 h. Elevation of corticosterone in both plasma and inflammatory exudate appeared to be correlated, suggesting that the exudate corticosterone was derived from the blood circulation. Injection of exogenous histamine and PGE2 into the air pouch induced a significant increase in exudate levels of corticosterone. However, plasma corticosterone increased significantly only after histamine administration, although a slight increase was observed in those injected with PGE2. These findings thus suggest that endogenous histamine and PGE2 which are released during carrageenan-induced acute inflammation, as shown in our previous work, might be responsible for the increase of corticosterone in both plasma and inflammatory exudate.


[Effect of pan-retinal photocoagulation in iris neovascularization].

The authors were able to produce experimental rubeosis iridis in the rhesus monkey's eye on 5 days following occlusion of the major retinal vessels and persistent ocular hypotony. Histopathological examination revealed true neovascularization. This experiment attempted to see whether laser pan-retinal photocoagulation plays an inhibiting effect on the occurrence of rubeosis iridis or not. We first performed laser pan-retinal photocoagulation, and at the same time performed occlusion of the major retinal vessels and persistent hypotony to aid for rubeosis iridis. Clinically, rubeosis iridis appeared within 5 days. At 14 days, histological examination revealed vessels on the surface of the iris following pan-retinal photocoagulation treatment were covered by fibroblast and melanocyte, and their endothelial cells showed no fenestrations. This means that clinical rubeosis iridis is not true neovascularization, but dilatation of the iris vessels. Thus, it was confirmed that pan-retinal photocoagulation inhibits development of iris neovascularization.


The contribution of transrectal ultrasonography in the early diagnosis of prostate cancer.

Two hundred twenty asymptomatic males, aged 55 to 75 years old, underwent transrectal ultrasonography of the prostate as part of a screening examination. Fifteen prostate adenocarcinomas were detected, 5 of which were nonpalpable. The biopsies were performed under sagittal ultrasound guidance. Serum prostatic specific antigen and prostatic acid phosphatase levels were also obtained from each patient. Nine of the patients were staged as B2, one patient as D2, 4 patients as A1 and one as A2. The use of transrectal ultrasonography as a screening tool must be further evaluated in a multicenter trial with a large number of patients.


[Correlation between volumetric endosonography and prostate weight. Variation according to histological type].

Correlation between endosonographic volumetry and prostatic weight, accuracy according to histopathology. We report a study over 50 patients who underwent TURP, demonstrating statistical correlation between endosonographic volumetry and prostatic weight. We observe a difference in accuracy according to histopathology and we discuss the reliability of the technique. We conclude that variability is due to the sensitivity of the examination.


[Prostatic cancer after transurethral resection for benign prostatic hypertrophy].

Five cases of prostatic cancer developed after transurethral resection of prostate for benign hypertrophy are reported. Duration of transurethral resection of prostate (TUR-P) to diagnosis of prostatic cancer ranged from one year and seven months to seven years and two months, on average four years and seven months and frequency of prostatic cancer after TUR-P was estimated at 1.2%. Four of five patients complained of macroscopic hematuria. The cystourethrogram showed the mass protruded in the dilated prostatic urethra or bladder-neck in four patients (80%), a remarkable finding, and four cases were at stage D. Risk of development of prostatic cancer is not decreased even after prostatectomy and prostatic carcinoma diagnosed after TUR-P often advances in stage. Therefore, periodical examinations of the patients who had a prior prostatectomy are very important.


[A study on the mass screening system for prostatic diseases].

Between 1984 and 1990, a mass screening for prostatic diseases was carried out on men over 55 years old in cities, towns and villages in Toyama Prefecture, Japan. The total number of subjects examined in the primary study was 1,232, which was 17.7% of the males over 55 years old in these areas. The primary study consisted of inquiry concerning urination, digital examination of the prostate, transabdominal ultrasonography, and determination of tumor markers. A secondary study was indicated for 100 subjects (8.9%) suspected to have prostatic cancer and 169 (15%) suspected to have benign prostatic hypertrophy, but only 92 (35%) of them were actually examined. Prostatic cancer was histologically diagnosed in 3 subjects (0.3%), and benign prostatic hypertrophy was established in 56 subjects (4.5%), who were referred to urologists. Though a high percentage of the population was covered by the primary study the percentage of subjects who received the secondary study among those in whom it was indicated was low. This probably was a reason for the low detection rate of prostatic cancer. An improved system is considered to be needed to increase the efficiency of mass screening for prostatic diseases.


[A case of tranilast-induced cystitis with transient ECG changes].

A case of tranilast (Rizaben)-induced cystitis accompanied with possibly hypereosinophilic heart syndrome was described. A 75-year-old male, who had been taking tranilast for allergic dermatitis for two months, was admitted for severe bladder stimulating symptoms which was unresponsive to antibiotic therapies. Clinical examination revealed tenderness of the prostate, aseptic pyuria, eosinophilia, liver dysfunction and electrocardiographic disorders including atrial fibrillation, T-wave inversions and lowered ST segment without any cardiac symptoms. Cystitis symptoms, pyuria, eosinophilia and liver dysfunction improved within several days after discontinuance of tranilast, and ST-T changes on ECG gradually normalized within a few months. Tranilast-induced cystitis has been demonstrated as a type of eosinophilic cystitis. Since pathologic findings of eosinophilic cystitis and hypereosinophilic heart syndrome are markedly similar and all symptoms and signs disappeared after deprivation of tranilast, it appears likely that eosinophilic inflammation was induced to the heart, liver, bladder and prostate of the current patient by tranilast.


[Antiandrogen therapy of benign prostatic hypertrophy: clinical effects of allylestrenol evaluated by transrectal ultrasonographic measurement].

A multicenter trial was carried out on 100 patients with benign prostatic hypertrophy to elucidate the efficacy of anti-androgen therapy with allylestrenol (AE). AE was administered at a daily dose of 50 mg for 16 weeks to the patients and its efficacy was evaluated with subjective symptom scores, residual urine volume and uroflow rates. The effects of AE on prostatic volume and morphology were evaluated using transrectal ultrasound. Of these patients 65 completed the protocol, and only three patients withdrew from the study owing to side effects. Very modest adverse effects on sexual performance were seen in one patient. In this study, significant beneficial effects of AE on symptom scores, residual urine, maximum flow rate, and prostate size were demonstrated. However, volumetric reduction was not associated with urodynamic improvement. Prostatic shape was not changed throughout the study. These findings suggest that allylestrenol can be used as an alternative to prostatectomy in patients who are at high risk for surgery.


[Pure yolk sac tumor of the testis with brain metastasis: report of an adult case].

Herein we report an adult case of pure yolk sac tumor with brain metastasis. The patient was a 37-year-old male who presented with indulation of his left scrotum for 10 months. The plain computerized tomographic (CT) scan on entry demonstrated tumor metastasis to his lung and liver and serum alpha-fetoprotein (AFP) level was 786 ng/ml. Five days after admission, he developed hemiplegia secondary to the cerebral metastasis and hemorrhage. After chemotherapy and operation of right-posterior lobectomy, PVB (cisplatinum, vinblastine, bleomycin) chemotherapy produced a complete remission and the elevated serum AFP was normalized. However, the second course of chemotherapy had to be discontinued because of drug-induced hepatitis. He died of massive tumor metastasis to his brain 6 months after craniotomy.


[Clinical effects of distigmine bromide (Ubretid), a cholinesterase inhibitor, on micturition disturbance by benign prostatic hypertrophy--comparative study of distigmine bromide and the combination of distigmine bromide and adrenergic blocker].

We report the results of a comparative study on the clinical efficacy of the single use of distigmine bromide and its combined use with prazosin hydrochloride in the treatment of benign prostatic hypertrophy. The single use and combined use groups were administered 10 mg/day of distigmine bromide and the same with 1 mg/day of prazosin hydrochloride for a period of 8 weeks respectively. In the single administration group, marked improvement was found in one patient (9%), moderate improvement in 4 patients (36.3%), slight improvement in 3 patients (27.2%) and aggravation in 3 patients. In the combined use group, marked improvement was found in one patient (11.0%), moderate improvement in 5 patients (55.5%), and slight improvement in 3 patients (33.3%). No significant differences were found in the improvement rate between the two groups. However, significant improvements were found in both groups for the subjective symptoms of urinary disturbance, diurnal and nocturnal frequency. As a result of the examination of objective findings, a significant decrease in residual urine ratio was also shown in both groups, while significant improvement for average flow and maximum flow rates were found in only the combined use group. In conclusion, distigmine bromide and distigmine bromide+prazosin hydrochloride are considered very useful for the treatment of miturition disturbance due to benign prostatic hypertrophy.


Self-expanding metal stents for palliative treatment of malignant ureteral obstruction.

We studied the immediate and long-term efficacy of the Wallstent device in the treatment of ureteral obstruction caused by malignant disease. In 23 patients (30 ureters), self-expanding metal stents were implanted endoscopically (n = 23), percutaneously (n = 5), or bidirectionally (n = 2) because of extrinsic malignant ureteral obstruction. Patients who met the following criteria were selected for stent implantation: (1) life expectancy of at least 6 months, (2) current polychemotherapy, (3) increasing levels of serum creatinine, and (4) severe clinical signs and symptoms associated with hydronephrosis. Obstruction was diagnosed by using sonography and excretory urography. After radiologic localization and dilatation of the stenosis, the Wallstent device was inserted. For 4 weeks, a double-J catheter inserted through the stent was kept in place in order to prevent obstruction by reversible hyperplastic reaction of the urothelium. Patients were followed up for 31 weeks (range, 3-75 weeks). Follow-up included sonography, excretory urography, and determination of serum levels of creatinine in all cases and furosemide scintigraphy and the Whitaker test in selected cases. Implantation of the Wallstent device was successful in 30 (97%) of 31 cases attempted. The survival rate was 81% after 6 months and 61% after 8 months. The primary patency was 83% after 30 weeks. Complications were macrohematuria (one patient) and incrustation (two patients). No infection and no migration or compression of the stent were observed. Implantation of a Wallstent device is a safe and effective alternative to double-J catheter placement in tumor-associated ureteral obstruction.


Scabies.

Scabies is highly contagious and is usually transmitted by direct personal contact. It typically presents as an intensely pruritic eruption. Atypical presentations are common in Norwegian scabies and in childhood scabies. Infestation is documented by visualizing the mite, its eggs or scybala on low-power microscopy. The treatment of choice is 5 percent permethrin cream, used in a single application at bedtime and removed the next morning.


Arrhythmias after cardiac transplantation.

The etiology and clinical significance of sustained arrhythmias, and atrial and ventricular premature complexes (APCs and VPCs, respectively) after heart transplantation are controversial. Fifty adult recipients surviving > 2 weeks were studied by continuous telemetry while in the hospital and by ambulatory electrocardiographic monitoring at 2, 4, 6, 12 and 24 weeks after transplantation. The median APC frequency was greater among subjects who experienced allograft rejection in the early postoperative period (0.7/hour, range 0 to 23) than among those who did not (0.2/hour, range 0 to 10.4) (p = 0.04). The APC frequency in all subjects decreased from 0.25/hour (range 0 to 23) early to 0/hour (0 to 14) later (p = 0.04). Atrial flutter was the most frequent sustained arrhythmia; it was recorded in 5 of 21 rejectors and in 1 of 29 nonrejectors (p = 0.04), and 11 of 16 episodes (69%) were related to acute rejection temporally. VPCs were recorded in all patients early after transplantation, but the median frequency subsequently decreased from 4.6/hour (range 0.5 to 470) early to 1.25/hour (range 0 to 225) later (p < 0.001). VPC frequency was unrelated to rejection. Sustained ventricular tachycardia was recorded once and was caused by the proarrhythmic effect of flecainide. Thus, APCs and VPCs occur frequently after transplantation. Frequent APCs are associated with rejection, whereas the main determinant of VPC frequency is time after transplantation. Atrial flutter is closely associated with rejection and should be regarded as an indication for endomyocardial biopsy. Ventricular tachycardia occurs seldom, and in this study was due to proarrhythmic drug effects.


Electropharmacologic effects and pharmacokinetics of almokalant, a new class III antiarrhythmic, in patients with healed or healing myocardial infarcts and complex ventricular arrhythmias.

The electropharmacologic effects and pharmacokinetics of almokalant, a new class III antiarrhythmic, were investigated in a randomized, placebo-controlled, double-blind study, and efficacy was evaluated. Ten post-myocardial infarction patients with complex ventricular arrhythmias were included and received, in randomized order on consecutive days, 4.5 mg (12.8 mumol) of almokalant or placebo intravenously over 10 minutes. One patient received infusion at a higher rate and developed self-terminating torsades de pointes. In the remaining 9 patients the corrected QT interval increased significantly: At the end of placebo infusion the corrected QT was 445 +/- 18 ms and after almokalant 548 +/- 53 ms (p = 0.0015). The signal-averaged electrocardiographic parameters did not change. The number of ventricular premature complexes decreased significantly during the first 15 minutes after almokalant infusion (p = 0.04). No additional proarrhythmic or other significant adverse events were noted. The almokalant plasma concentration showed a biphasic decrease with an elimination half-life of 2.4 +/- 0.1 hours. Almokalant was rapidly cleared from the body with a clearance of 11 +/- 1 ml/min/kg. When given with certain precautions almokalant appears safe and well-tolerated and may be antiarrhythmic by prolonging refractoriness.


Comparison between cetirizine and terfenadine: time-response study.

Six young healthy volunteers were used as experimental models to study the efficacy of cetirizine 10 mg and terfenadine 60 mg with regard to the onset of action and duration of the peripheral antihistaminic effect (cutaneous activity). For this purpose, 10 micrograms of histamine were used administered as intradermal injection at the internal border of the forearm at times 0', 30', 60', 90', 120', 180', 240', 360', 480' and 24 h after the intake of the drug, with a minimum interval of 7 days between one drug and the other. The inhibition of the cutaneous activity of histamine was assessed by planimetry of the papule transferred to adhesive paper. Both antihistamines were well tolerated by the oral route and our patients did not refer any anticholinergic side effects nor sedation, which are classically described in relation to first generation anti-H1 drugs. When comparing both antihistamines as to their ability to inhibit the response, there are no differences between them at 30', but from this time point up to 24 h cetirizine inhibits significantly more than terfenadine the response to histamine; cetirizine achieves its maximal effect at 180', while terfenadine does so at 240'; both drugs maintain their maximal effect antil 480' and, as was previously mentioned, at these doses cetirizine shows a higher percentage of inhibition than does terfenadine at equal time points.


Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan.

Previous observations have shown that oral administration of 5-hydroxytryptophan (5-HTP) without dietary prescriptions causes anorexia, decreased food intake, and weight loss in obese subjects. To confirm these data over a longer period of observation and to verify whether adherence to dietary restriction could be improved by 5-HTP, 20 obese patients were randomly assigned to receive either 5-HTP (900 mg/d) or a placebo. The study was double-blinded and was for two consecutive 6-wk periods. No diet was prescribed during the first period, a 5040-kJ/d diet was recommended for the second. Significant weight loss was observed in 5-HTP-treated patients during both periods. A reduction in carbohydrate intake and a consistent presence of early satiety were also found. These findings together with the good tolerance observed suggest that 5-HTP may be safely used to treat obesity.


Patterns of keratin 19 expression in normal, metaplastic, condylomatous, atrophic, dysplastic, and malignant cervical squamous epithelium.

Keratin 19 (K-19) expression has been strongly correlated with dysplasia in oral epithelium. Expression of K-19 was evaluated by immunoperoxidase staining in formalin-fixed normal ectocervical tissue, normal endocervical tissue, cervical dysplasia, squamous metaplasia, atrophic epithelium, cervical condylomas, and invasive carcinoma to determine if a correlation of K-19 expression with dysplasia was present in the cervical epithelium. Uniform expression of K-19 was seen in endocervical epithelium and in the basal layer of normal ectocervical epithelium in all areas where these epithelia were present. Cervical dysplasia without associated condylomatous changes showed increased expression of K-19 in suprabasal epithelium, corresponding to the level of immature cells. Squamous metaplasia was characterized by scattered cells with increased staining (patch-quilt pattern). There was considerable overlap in the patterns of K-19 expression in dysplastic and metaplastic epithelium. Thus K-19 staining pattern could not be used as a distinctive marker for dysplasia in the cervical epithelium. Atrophic epithelium showed a characteristic uniform but low-level expression of K-19 in suprabasal areas. This pattern may be of diagnostic use in differentiating atrophic lesions from dysplasia. Condylomas showed focal loss of K-19 in the basal layer, suggesting induction of premature differentiation in the basal layer by human papillomavirus infection. Invasive carcinomas showed variable patterns. K-19 is a marker of immature cervical squamous epithelium, with generally distinctive but sometimes overlapping patterns of expression in various diagnostic categories.


[Occupational hypersensitivity to spiramycin. Report of a case].

A case report of occupational hypersensitivity to Spiramycin. Rhinoconjunctivitis and spasmodic cough are reported in a 34 year-old female handling spiramycin powder in a pharmaceutical factory. The symptoms appeared within the first few hours of coming into contact with the drug and continued for several hours after leaving her place of work. The patient had no personal case history of atopy. Results for prick-test with extracts using a concentration of 1/100 (w/v) were positive, as were results por intradermical tests with a solution using a concentration of 1/10.000 (w/v). The diagnostic was confirmed with the application of a nasal provocation test. Our criteria to determine positivity to this test was according to Bachman (1) and the European Committee of Rhinomanometry. On our suggestion the patient was transferred to another section of the pharmaceutical company whereupon all symptoms disappeared immediately and no further allergic reactions to drugs were registered. This case suggest that reactions to a chemical product may involve immunological mechanisms.


Follicular lymphoma of compartmentalized small cleaved center cells and mantle zone lymphocytes. Evidence for a common derivation.

The authors have observed a unique case of follicular lymphoma in which the central zones of neoplastic nodules were composed predominantly of small cleaved cells (SCC) that were surrounded by small lymphoid cells proliferating in wide mantles as in mantle zone (MZ) lymphoma. The central SCC component displayed a follicular SCC lymphoma-like phenotype (IgD-, CD10+, CD5-, CD68-), whereas the neoplastic cells of the peripheral zones had an MZ lymphoma-like phenotypic profile (IgD+, CD10-, CD5+, CD68+). In extranodal involved tissues, either follicular or diffuse (leukemic-like) patterns of lymphoma infiltration were noted. Flow cytometric analyses showed in the bone marrow or the peripheral blood two leukemic B cell populations, one mimicking the phenotypic profile (IgM+, IgD+, CD5+, CD10-, Leu8-) of small lymphoid cells with MZ-like features, and the other with phenotypic features (IgM+, IgD-, CD5+, CD10+, Leu8+) intermediate between those of MZ-like cells and those of the SCC component (follicular center-like) detected in the lymph node. Immunomagnetic sorting and gene rearrangement studies indicated that both CD10+ and CD10- B lymphocytes and lymph node neoplastic B cells shared the same clonal origin. This unusual follicular lymphoma can be viewed as the result of the proliferation of a single follicular progenitor capable of differentiating toward both a germinal center and an MZ phenotype. The simultaneous presence in the same patient of at least three neoplastic B-cell populations at different maturation stages, encompassing follicular center and MZ phenotypes, and showing the same clonal derivation, indicates a close lineage relationship between follicular SCC and MZ lymphomas.


Kindergarten readiness after extreme prematurity.

To assess kindergarten readiness among survivors of extreme prematurity and to identify predictors of special education requirements. Historic cohort design. Regionalized tertiary pediatric center. One hundred forty-nine (97%) of 153 children who were alive at follow-up (mean +/- SD age, 52.7 +/- 9.9 months). Study cohort included infants (gestation, 23 to 28 weeks), born between 1983 and 1986 (N = 194), who were alive at follow-up (N = 153, 79% survival). None. Standardized neurodevelopmental and psychometric evaluations were administered by a multidisciplinary team that was blinded to the neonatal course. Thirty-one children (21%) had major neurodevelopmental impairments. By using the McCarthy Scales of Children's Abilities for children free of major impairments, 61 (63%) had one or more minor neurodevelopmental impairments noted. Half of the surviving children were thought to require special education resources at kindergarten entry. Multivariate logistic regression identified three significant predictors of special education: low socio-economic status, nonwhite race, and male gender. Social and demographic variables were associated with minor neurodevelopmental impairments and special education requirements among extremely premature children. Continued developmental follow-up and targeted interventions to reduce the risk of educational underachievement appear to be warranted.


Elevated interleukin-6 and gamma-globulin during interferon therapy of hepatitis B.

A 49-yr-old man with chronic hepatitis B manifested hypergammaglobulinemia, lymphadenopathy, and a high serum interleukin-6 level following treatment with recombinant human alpha-interferon. One month later, when the patient was treated with natural beta-interferon, serum levels of interleukin-6 and gamma-globulin increased again. The serum gamma-globulin decreased to the pretreatment level after discontinuation of interferon therapy. The serum alanine aminotransferase level remained normal for 6 months. In this case, hypergammaglobulinemia and lymphadenopathy, as well as the elevated serum interleukin-6 level, were considered to be signs of highly enhanced humoral immunity related to alpha- and beta-interferon therapy.


Immunologic markers of progression to acquired immunodeficiency syndrome are time-dependent and illness-specific.

Since prevalent cohorts may be biased by the duration of human immunodeficiency virus (HIV) infection (onset bias), it is useful to assess the potential predictive value of markers in incident cohorts of HIV-positive subjects for whom the date of seroconversion is known or can reliably be estimated. Of 131 homosexual men with HIV-1 seroconversion from New York City and Washington, DC, who were evaluated annually beginning in 1982, 60 developed acquired immunodeficiency syndrome (AIDS) by the end of 1989. The prognostic significance of immunologic markers (proportion of CD4+ T-lymphocytes, neopterin, beta 2-microglobulin, serum interferon, and anti-p24 antibody) and of a virologic marker (HIV p24 antigen) was determined using measurements made at defined time intervals after the known or estimated date of HIV seroconversion. When measurements made 3 years after seroconversion were used, all markers except anti-p24 antibody were found to be significant estimators of AIDS risk in univariate analyses. In multivariate Cox regression modeling, the maximum information was obtained by including neopterin, interferon, and the CD4+ T-lymphocyte proportion. The predictive value of markers after HIV seroconversion could change considerably from one interval to another. Elevated levels of beta 2-microglobulin and neopterin significantly predicted the development of Kaposi's sarcoma. These two markers were highly correlated (r = 0.74). The authors conclude that immunologic markers can be important for an HIV staging system for estimating prognosis and facilitating early therapeutic intervention in HIV-positive patients.


CD5 B lymphocyte antigen in monoclonal gammopathy.

Because B lymphocytes bearing the CD5 antigen have been involved in many B-cell malignancies, we have investigated the presence of the CD5 B-cell antigen on B and plasma cells in monoclonal gammopathy. Quantification of CD5 B cells was made in the peripheral blood of seven individuals with monoclonal gammopathy of undetermined significance (MGUS) and in that of 21 patients with multiple myeloma (MM). The bone marrow of ten patients with MM was also studied. Patients with progressive MM presented a significant reduction in both B and CD5 B lymphocytes (i.e., percentages and absolute numbers), when compared with individuals with MGUS and patients with stable MM. These latter individuals and patients did not differ from healthy donors. No CD5 B cells were found in the bone marrow of patients with MM. Moreover, no CD5 antigen could be detected on eight freshly established human myeloma cells lines including six totally dependent on interleukin-6. However, it was weakly expressed on two standard myeloma cell lines not requiring exogenous interleukin-6 (i.e., RPMI 8226 and U 266). In conclusion, our data show mainly an overall reduction of the polyclonal CD5 B lymphocytes similar to what is observed for the other polyclonal B lymphocytes in patients with active MM. Finally, the expression of the CD5 antigen human myeloma cell lines is not constant.


Detecting of the minimal residual disease contaminated in peripheral blood stem cell transplantation in the B-cell malignant lymphoma patients.

For sufficient collection of hemopoietic stem cells from peripheral blood for autologous peripheral blood stem cell transplantation (PBSCT), four patients with B-cell-type non-Hodgkin lymphoma (B-NHL) were examined for the appearance of circulating hemopoietic progenitors in blood (PSC) during the hemopoietic recovery phase following marrow ablative therapy in combination with or without administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Each patient received only chemotherapy in the first course, and rhG-CSF (1 microgram/kg/day) was administered for 14 consecutive days from the last day of the second chemotherapy. In the second chemotherapy course with rhG-CSF administration, white blood cell (WBC) counts demonstrated two peaks, and the appearance of granulocyte-macrophage precursor cells (CFU-GM) in blood at the maximum level was coincident with the second peak of WBC elevation. Erythroid precursor cells (BFU-E) were also detectable in blood after chemotherapy but the peak level was not enhanced by the use of rhG-CSF. To determine whether the minimal residual disease (MRD) cells were contaminated in PSC corrected from blood, kappa-lambda imaging (KLI) analysis was performed to detect the malignant B-cell population (mBp) before and after chemotherapy. No mBp was found in two of four patients in blood, although three of them were involved with mBp in bone marrow. The presence of mBp was detected in two patients both before and after chemotherapy, even though these cells were hardly detected morphologically, suggesting the necessity of judging for the incidence of contamination of MRD cells when collecting PSCs.


Human interleukin-9 supports formation of a subpopulation of erythroid bursts that are responsive to interleukin-3.

We have investigated the biological activities of recombinant human interleukin-9 (IL-9) on enriched hematopoietic progenitors, alone or in combination with other cytokines, including Epo, G-CSF, IL-3, and GM-CSF, under serum-containing and serum-free cultures. IL-9 alone did not support colony formation. However, IL-9 plus Epo induced erythroid burst (BFU-E) formation derived from peripheral blood (PB) progenitors. Delayed addition experiments demonstrated that a part of bone marrow (BM) derived BFU-E, which seems to be immature, only responded to IL-9 and formed erythroid bursts. The burst-promoting activity (BPA) of IL-9 was confirmed using neutralizing aIL-3, aGM-CSF, and aIL-9 antisera and serum-free culture. IL-9 supported a part of BFU-E population that respond to IL-3, which was almost identical to the number of BFU-E supported by GM-CSF. IL-9 had no additive effect on erythroid and mixed colony formation supported by IL-3. In contrast, IL-9 showed an additive effect on erythroid burst formation supported by GM-CSF in serum-free culture. These data suggest that IL-9 and GM-CSF act on distinct IL-3-responsive BFU-E population. In addition, delayed addition experiment clearly demonstrated that IL-9 supports survival and the early stage of proliferation of BFU-E. These results led us to propose that IL-9 possibly acts as a BPA and selectively supports a subpopulation of early class of BFU-E that respond to IL-3.


Black beta-thalassemia homozygotes with specific sequence variations in the 5' hypersensitive site-2 of the locus control region have high levels of fetal hemoglobin.

We have sequenced the 5' hypersensitive-2 (5'HS-2) site of the locus control region (LCR) and the promoters of the two gamma-globin genes located on chromosome 11 of a black patient with mild beta-thalassemia (beta-thal) major due to a homozygosity for the C----T mutation at position -88 of the beta promoter and with a high Hb F level. Sequence variations in the 5'HS-2 were the same as observed for the beta s chromosome with haplotype number 3, while most of the G gamma promoter and the A gamma promoter had sequences similar to that of the beta S chromosome with haplotype number 19. This atypical haplotype (number 19A) is apparently associated with an increased gamma chain production which is particularly evident during periods of severe hematopoietic stress. Additional studies on relatives of the proband and on 10 unrelated black beta-thal homozygotes with either the C----T mutation at -88 or the A----G mutation at -29, confirm the possible importance of the sequence differences in the 5'HS-2, and also suggest that at least two additional factors, namely a C----T mutation at position -158 of the G gamma promoter and a relative deficiency in alpha chain synthesis play a (perhaps less important) role in the increased Hb F synthesis in these patients.