[The use of a hydroxylapatitie-based biogenic composite material for eliminating intraosseous cavities]. A rational method to remove the intraosseous cavities by cystectomy, making use of biogenic composite material Colap, has been developed. This material stimulates reparative osteogenesis, creates the optimal conditions for bone wounds healing. A total of 46 patients were operated on for large extensive cysts of the jaws with filling of the postoperative bone defects with the biocomposite. Examinations carried out in 6-10 months have shown complete reparation of bone tissue in the postoperative cavities.


[Outcome of gestation of 32 pregnant women with toxoplasma and cytomegalovirus infection]. In an attempt to investigate the harmful effects of the infection of Toxoplasma and associated with cytomegalovirus on the fetus infection acquired transplacentally during their mothers' pregnancy sera from 1000 pregnant women were tested for antibodies to both pathogens and the circulating antigen of Toxoplasma by using ELISA. The test was positive (titre > or = 1:60400) in 32 of 1000 cases. Judging from the sero-positive results together with the case history, clinical manifestations and B-scan results, the 32 cases were advised to end their pregnancy. Necropsy and pathological examinations of the foetuses revealed stillborn foetus, hydrocephalus, acephalus, pleural effusion, ascites and other congenital malformations. Toxoplasma gondii were found in the tissues of 21 fetuses.


[The effect of hydroxylapatite on the experimental healing of the tooth socket]. Synthetic hydroxylapatite, a drug made in this country, enhanced reparative osteogenesis if introduced in the dental well of a white rat. The regenerate represented solid bone structure in 4 months after tooth removal.


[Surgical treatment for small cell carcinoma of the lung. Report of 102 cases]. One hundred and two patients with small cell carcinoma of the lung were operated on from June 1965 to December 1990. The five-year survival rate of the patients who underwent resection only was 9.4% (5/53). The five-year survival rate of those who received operation, chemotherapy and radiotherapy was 25.0% (1/4). There was a remarkable difference between the two groups (P < 0.01). Operation with adjuvant chemotherapy or radiotherapy is the first choice of treatment in patients with small cell carcinoma of the lung. Stage I and stage II cases should be considered as Operative candidates. Chemotherapy should be given before and after operation. Postoperative radiotherapy Should be given to the patients with residual Cancer.


[Gastric emptying and metabolic acidosis. II. Study, in an experimental model in rats, of gastric retention of a sodium bicarbonate solution]. The gastric emptying of a 0.25 M sodium bicarbonate solution was studied in rats with metabolic acidosis induced by a previous (6 hours) orogastric infusion of a 0.5 M ammonium chloride solution. Two control groups were used: one previously infused with 0.5 M sodium chloride and the other with water, in the same volume that further solutions. Every animal was fed with 2 ml/100 g of its weight of these solutions. The test meal (bicarbonate solution) was utilized containing 6 mg% red fenol as a marker. The gastric retentions were determined 6 hours after those first meals at 5, 10, 20 and 30 minutes. The results demonstrated that the gastric retentions of the bicarbonate solution were significantly lower in the acidotic group than that one of water group (at 20 minutes) and that one of the sodium chloride (at 10, 20 and 30 minutes). The data here presented suggest that metabolic acidosis accelerates the gastric emptying of a sodium bicarbonate solution.


[Peripheral nerves injection injury: the clinical and experimental study]. The results of operative management of peripheral nerve postinjection injuries in 58 patients are reported. Neurolysis is one effective method in treating nerve postinjection injuries with excellent and good results observed in 64.6 percent of patients in this series. We also investigated the early changes in neurophysiological, histological and ultrastructural studies in the peroneal nerve of the rabbit. The results from early exploration and 0.9% NaCl irrigation were compared with those from late extraneural and intraneural neurolysis. The results showed that the injury occurs early in the nerve following intrafacicular injection and may proceed quickly to a certain degree of severity, so timely operation is advisable early incision of the epineurium with saline irrigation is superior to the neurolysis in treating nerve injuries as proved by the experimental study which suggests that the former can be used as an emergency operation for the management of this type of nerve injuries.


[Gastric emptying and metabolic acidosis. III. Study of gastric retention of a sodium citrate solution using an experimental model of metabolic acidosis in rats]. The gastric emptying of sodium citrate solution 0.25 mEq/ml was studied in rats with metabolic acidosis induced by orogastric infusion of 0.5 M ammonium chloride solution. Two control groups were used: one infused with 0.5 M sodium chloride and the other with water. The 3 solutions content was 2 ml/100 g weight of the animal. Six hours after the infusion, there was a moderate metabolic acidosis in the group with ammonium citrate. This 6 hour interval marked the beginning of the gastric emptying study. The test meal (sodium citrate 0.25 mEq/ml) was utilized containing 6 mg% red fenol as a marker. The gastric emptying of sodium citrate was studied at 5, 10, 20 and 30 minutes after the infusion, and the results showed no differences between the 3 groups. The data suggest that the duodenal receptors to pH were more effective do determine the pattern of gastric response than the acidosis.


Isoniazid induced neuropathy in slow versus rapid acetylators: an electrophysiological study. Clinical, biochemical and nerve conduction studies were performed in 100 cases of tuberculosis taking isonicotinic acid hydrozide (isoniazid) for more than 12 weeks. Electro-physiological studies were carried out in a similar number of normal age and sex matched controls. In 16 percent of cases an abnormality was documented in the motor nerve conduction velocity, amplitude and terminal latency of the common peroneal, ulnar and median nerves; of these, only two patients had objective evidence of neuritis. The occurrence of isoniazid neuropathy was found to be more in the fourth decade of life (10 of 16), in those who had taken the drug for over six months (13 of 16), and in 'slow' inactivators (10 of 16).


Combined effects of flavonoids and acyclovir against herpesviruses in cell cultures. The combined antiviral effects of some flavonoid compounds and acycloguanosine (acyclovir, Zovirax) were studied on the multiplication of herpes simplex virus types 1 and 2 in HEp-2 cells and on pseudorabies (Aujeszky) virus in chick embryo fibroblast cells by the yield reduction method. The flavonoids quercetin, quercitrin (quercetin-3-L-rhamnoside) and apigenin exhibit antiviral activity against these herpesviruses, and acyclovir is currently one of the most effective antiherpetic agents. In these studies, the simultaneous application of flavonoids with acyclovir resulted in an enhanced antiviral activity. A mathematical formula was used to interpret the drug interaction, resulting in FIC (fractional inhibitory concentration) indices. Meaning a synergic interaction, all combinations exhibited synergy, FIC values of 0.6-0.8 being commonly observed.


[Inhibitory effect of tumor growth by methionine-enkephalin]. Methionine-enkephalin (Met-Enk) is an endogenous opioid pentapeptide derived from the prohormone proenkephalin A, present in neuroendocrine and hematopoietic cells. Enkephalins are known to play an important role on the processes of induction, activation and control of immunomodulatory events. Met-Enk has been considered a potent antitumoral agent. The present study shows that Met-Enk exerts an inhibitory effect on the growth of a macrophage derived fibrous histiocytoma (MC-II) inoculated intradermally into BALB/cJ mice. Such effect was mainly influenced by the protocol, route of administration and concentration of Met-Enk used for treatment. Neither higher doses of Met-Enk injected intracerebrally or subcutaneously, nor the use of various protocols of treatment, did modify the process of tumorigenesis. In contrast, low dose (0.25 mg/kg) of Met-Enk injected intracerebrally together with tumor inoculation, significantly reduced tumor growth and prolonged survival rate.


O6-methylguanine-DNA methyltransferase activity and sensitivity of human tumor cell lines to bis-chloroethylnitrosourea. The relationship between O6-methylguanine-DNA methyltransferase (O6-MT) activity and the sensitivity of 4 kinds of human tumor cell lines to bis-chloroethylnitrosourea (BCNU) was evaluated. The results demonstrated that cellular resistance to BCNU was linearly correlated with O6-MT activity, suggesting that O6-MT plays an important role in repairing DNA damage induced by BCNU. Furthermore, the depletion of O6-MT activity by streptozotocin (STZ) pretreatment and its effect on the cell's sensitivity to BCNU were investigated. O6-MT activity could be efficiently reduced, and sensitivity to BCNU was subsequently increased significantly. There was also a linear correlation between depletion of O6-MT activity and enhancement of BCNU's cytotoxic effects. These results indicate that O6-MT might constitute the molecular basis of cellular resistance to BCNU, and a combination of STZ and BCNU may result in better therapeutic effects.


[Itraconazole action on Toxoplasma gondii]. With the purpose to increase our knowledge about the spectrum of therapeutic action of itraconazole, the activity of a new triazolic derivative against Toxoplasma gondii was studied in vivo and in vitro with the aid of an experimental infection model in mice. The trial also aimed at a possible improvement of the therapy of toxoplasmosis in regard to safety and dosing easiness. The present study has not shown significant activity of itraconazole against Toxoplasma gondii, differing from a previous observation that showed it's activity against Trypanosoma cruzi.


Prospective study on the diagnosis of hepatocellular carcinoma by using alpha-fetoprotein reactive to lentil lectin. In order to study the changes in AFP reactive to lentil lectin (AFP-R-L) during the development of hepatocellular carcinoma (HCC) and its clinical significance, AFP-R-L was monitored in 64 patients by using 20-400 ng/L AFP and negative imaging localization. AFP-R-L was determined by using affino-crossed-immunoelectrophoresis autoradiography. AFP-R-L above 25% was considered positive for the diagnosis of HCC. Over a follow-up of 3-31 months, 32 patients developed HCC. The positivity of AFP-R-L was 59.4% in the HCC group at the first assay. The accuracy of using positive AFP-R-L values to predict HCC was 95.0%. Increased AFP-R-L levels appeared 3-24 months earlier than did positive imaging location. The results suggest that positive AFP-R-L values can predict the development of HCC.


Effects of human HSS on hepatocyte and hepatoma cell proliferation and D-GAL induced acute liver failure. Human hepatic stimulator substance (HSS), an organ-specific and heat-stable factor which differs from insulin, glucagon and EGF, has been partially purified from aborted human fetal livers. It was found to stimulate DNA synthesis of human hepatocytes. AH22 hepatoma cells responded dose-dependently. HSS was also found to enhance the survival of D-GAL intoxicated rats as compared to control (62.5% vs. 26.1%). Our results suggest that human HSS is very similar to that in animals.


[Indirect ultramicroElisa for the detection of total antibodies against cytomegaloviruses in human blood]. We have standardized an indirect ultramicro ELISA assay for detecting antibodies to human Cytomegalovirus (CMV) using human serum samples (UMELISA CMV). The optimal concentration of coating antigen (30 ug/ml), serum dilution (1:40) and anti-human conjugate working dilution (1:1500), were determined by a check board titration method. The UMELISA CMV was compared with the latex agglutination test for antibodies to CMV (Dupont de Nemours) and with an indirect immunofluorescent method. The results have showed the high coincidence, sensitivity and especificity of the proposed assay regarding the two methods compared with, and supporting its use either for a blood donors screening or in the serological diagnosis of this infection by paired serum samples.


Studies on the immunogenicities of intertypic chimeric polioviruses. To study the relationship between structure and antigenicity, two hybrid viruses, XF414 and XF3, were constructed. In XF414, N-Agl of PV1 was replaced by N-Agl of PV2; while in XF3, N-Ag1 of PV1 was replaced by N-Ag1 of PV3. In this study, XF414 and XF3 were cultured on a large scale in primary monkey kidney cells. The viruses were concentrated with PEG, purified with chloroform and Sepharose 2B and inactivated with formaldehyde. Their bivalent antigenicity was confirmed by neutralization inhibition test, immunoelectron microscopy, and rabbit immunization. It was also shown that both XF414 and XF3 can elicit bivalent neutralizing antibodies and that the bivalent antigenicities are not destroyed by formaldehyde inactivation. Such a study can provide a basis for the development of multivalent picornavirus vaccines.


[Blastomycosis of the cervicofacial area: a review of the literature and case report]. A literature review concerning blastomycosis has been conducted. The involvement of the head and neck area appears to be very unusual, on the basis of autoptic observations. The most common diagnostic and subsequent therapeutic mistakes are pointed out. A new case is described and its clinical appearance, symptoms, diagnostic work up and therapeutic approach are discussed. This case report is of interest for three reasons: the rarity of this disease in our country, the possibility of confusing a Blastomyces infection with a cryptococcal one [correction of criptococcosy] and finally the therapeutic response to a new drug, not yet commercialized in Italy.


[Studies of free radical metabolism in patients with cor pulmonale]. The levels of free radicals in the whole blood of the patients with cor pulmonale were determined using the method of electron spin resonance (ESR). The concentrations of serum SOD were determined using RIA. The concentrations of the MDA, vitamin E, selenium and the activities of the SeGSHPx, CAT of the patients were also measured using biochemical methods. The results showed that the level of free radical in the whole blood and serum MDA, SOD increase if compared with that of control group. The activities of SeGSH-Px, CAT and the concentration of vitamin E in serum of the patients are in lower level. These indicate that there is impairment in free radical metabolism of the patients.


[Lung sound analysis of upper airway obstruction]. The frequency spectrum of stridor was studied by the computer program in the patients with upper airway obstruction. The results showed that the peak frequency of respiratory sound increased significantly, the frequency spectrum got wider and removed to the high frequency area above 200Hz, the E ratio was smaller than 1. These changes were more apparent during inspiration than those during expiration. It is concluded that the stridorous sound could be determined exactly and quantitatively, and differentiated from wheezing by the spectral analysis.


[Evaluation of secondary hyperparathyroidism in the patients undergoing hemodialysis--focused on parathyroid hormone assay system]. We evaluated the degree of secondary hyperparathyroidism (SHPT) in the patients undergoing long-term hemodialysis treatment. Most patients showed improvement of SHPT by administration of the active vitamin D3 analogue. However, some patients developed overt SHPT even under intensive treatment. Pulse therapy with large dose of vitamin D3 for those who suffered from overt SHPT was an effective treatment modality at the initial stage, however, hypercalcemia which developed in the majority of the patients at the later stage of this treatment became an obstacle for the continuation of this treatment. Therefore, early detection of the hypersecretion state of parathyroid hormone (PTH) as well as earlier initiation of intensive therapy are important factors in preventing overt SHPT. Establishment of a suitable assay system for early detection of SHPT is an important task and the high sensitivity-PTH assay system may be the most desirable. Though diabetic patients were not likely to develop overt SHPT, this system could detect even the mild chronological increase of serum PTH level in diabetic patients. On the other hand, relatively earlier initiation of vitamin D3 therapy to the predialysis patients from the conservative treatment stage caused aggravation of deterioration of renal function. Therefore, we should be prudent to initiate vitamin D3 therapy on predialysis patients suffering from renal failure. Strict management of the patients by vitamin D3 as well as calcium supplement therapy along with evaluation of the serum PTH level is still an important measure to avoid overt SHPT.


[Epidemiological analysis of infectious mononucleosis as primary Epstein-Barr virus infection]. We report the characteristics of 45 Epstein-Barr virus (EBV)-infected patients visiting our hospital from 1989 to 1991 in comparison with 102 patients seen from 1981 to 1988. Cases of infectious mononucleosis (IM) increased especially in patients over 30 years old. They tended to have nonspecific symptoms and signs for IM such as general fatigue. Immunologically showed twice higher positivity for anti-EBV VCA-IgM antibody in the recent 3 years when compared to the previous 8 years. The patients with anti-EBNA antibody decreased in the recent 3 years. This may be due to early diagnosis as IM. EBV also causes atypical diseases. non-IM in this report, including hematological or neurological disorders. We indicated here the increased number and advanced age of patients with IM and early diagnosis as IM in the recent 3 years compared to the previous 8 years.


[Current status in hepatitis virus research]. Seroconversion from eAg to anti-e is frequently seen in the course of chronic hepatitis B infection. This phenomenon is closely related to mutation of the precore region; a G-to-A substitution of nucleotide position 1986 replaces tryptophan to translational stop codon. This mutant is responsible for the fulminant hepatitis or acute exacerbation of chronic hepatitis B. The hepatitis C virus shows a high rate of genome variations, especially at the envelope (E and NS1) region, where a neutralizing epitope is believed to exist. According to the sequence identity, the hepatitis C virus is divided into four subtypes. The virus appears to evolve separately in geographically different areas and the subtyping may have some clinical implications, such as in interferon treatment. Hepatitis E virus has three open reading frames and share the high nucleotide identity among strains isolated from Myanmar and China. Hepatitis E is endemic in the developing world and is not present in industrialized countries.


[Hepatic fibrosis and its serum markers]. As serum markers for hepatitis fibrosis, prolyl hydroxylase (PH), type III procollagen peptide (PIIIP), type IV collagen, mesenchymal metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP) and laminin are reliable for clinical application. PH, PIIIP, MMP, TIMP and LM are regarded as the marker of ongoing hepatic fibrosis. Type IV collagen and LM are indicative for the extent of hepatic fibrosis.


Dose-dependent vitamin D3, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3-induced hypercalcemia and hyperphosphatemia, and the correlative changes in the activity of ultimobranchial and parathyroid glands of the toad, Bufo andersoni Boulenger. Vitamin D3, 25(OH) vitamin D3 and 1,25 (OH)2D3 were administered daily to unfed male Bufo andersoni for 15 days which resulted in a significant hypercalcemia and hyperphosphatemia in a dose-dependent fashion. 1,25(OH)2D3 is more potent than the other metabolites. The treatment activated ultimobranchial gland but induced degenerative changes in parathyroid of the toads.


Fraser's syndrome.

Fraser's syndrome. A full term female baby at birth showed the features of Fraser's syndrome viz. upper lid coloboma, cryptophthalmos, abnormal groove over temporal region, dysmorphic facies, hypospadias and bilateral syndactyly. On ultrasound examination of the abdomen and left orbit, maldeveloped kidney and eyeball were found. Other siblings were not affected. The child died at the age of 3 months.


Role of phospholipids in the accessibility of LH/hCG receptors in porcine corpora lutea. The role of phospholipids in the interaction of LH/hCG with membrane-bound and water-soluble receptors was studied. Digestion of porcine corpora lutea (CL) membranes with phospholipase-A2 (PL-A2) diminished, in a dose dependent manner, both phospholipid concentration and binding of 125I-hCG to CL membranes. Treatment of the water-soluble LH/hCG receptor occurring in follicular fluid with PL-A2 produced no inhibitory effect on gonadotropin binding in spite of digestion of phospholipids. The decrease of the accessibility of LH/hCG receptors in CL membranes by PL-A2 was associated with a rise of the rigidity of membrane lipids. Dynamic properties of membranes were monitored by electron spin resonance of 5- and 16-doxyl stearic acid probes. These findings suggest that phospholipids play an important role in the accessibility of membrane-bound LH/hCG receptors, but are not involved in a direct interaction of gonadotropin with the binding sites.


Regulation of gene expression by fatty acids and fibric acid derivatives: an integrative role for peroxisome proliferator activated receptors. The Belgian Endocrine Society Lecture 1992. A group of receptors termed peroxisome proliferator activated receptors (PPAR), belonging to the nuclear hormone receptor supergene family, might be crucial in explaining how a diverse group of apparently unrelated chemicals induce peroxisomal proliferation and a change in the expression of several genes. The activation of these PPAR by peroxisome proliferators, as well as by fatty acids, might reconcile the apparent discrepancy between the two prevailing theories that explain peroxisome proliferation, i.e. the receptor and the fatty acid theory. Although the exact physiological role of PPAR is not yet known, these receptors might have a far more general function than strictly regulating peroxisomal gene expression by changing the expression of numerous genes in response to developmental and nutritional challenges. Much work, however, remains to be performed before a complete picture will emerge.


Membrane depolarization induced DNA synthesis in PU5-1.8 cells. Role of voltage-operated Ca2+ channel and protein kinase C. Incubation of non-excitable murine macrophage cell line PU5-1.8 in K+(140 mM)-Hepes buffer caused membrane depolarization as measured by bis-oxonol and 3,3'-dipropylthiodicarbocyanine. Depolarization of cell membrane produced an increase of intracellular free Ca2+ concentration ([Ca2+]i). Interestingly, short-term exogenously imposed membrane depolarization in PU5-1.8 cells in the absence of growth factors initiated the incorporation of [3H]thymidine or its analog, 5-bromo-2'-deoxyuridine, as well as the expression of early-response genes such as c-fos and c-myc. The expression of the proto-oncogene products seemed to be dependent on external Ca2+, and the [3H]thymidine incorporation was inhibited by nifedipine and verapamil at similar dosages as for Ca2+ inhibition. Calcium influx and [3H]thymidine incorporation could also be induced by Bay K 8644 or by gramicidin in the Na(+)-Hepes buffer. On the other hand, challenge of cells with sphingosine, staurosporine or 1-(5-isoquinolinesulfonyl)-2-methylpiperazine suppressed the K(+)-mediated DNA synthesis. Furthermore, preincubation of cells with phorbol 12-myristate 13-acetate (PMA) for 15 min in Na(+)-Hepes buffer enhanced the DNA synthesis. Yet, pre-incubation of cells with PMA or 1,2-dioctanoyl-sn-glycerol in K(+)-Hepes buffer suppressed the K(+)-mediated DNA synthesis and membrane depolarization. These observations suggest that a rise of [Ca2+]i is required for the initiation of DNA synthesis, and PKC may be functioning as a modulator with dual action at least on the level of ion conductance.


Nodus migrans: the case of the migrating knot. Flow-directed pulmonary artery catheters provide important information regarding intravascular volume status, cardiac function and vascular resistance. We describe an unusual complication of pulmonary artery catheterization in which a knot formed at the distal end was torn away from the catheter body and migrated from its original position in the right subclavian vein to a distal branch of the right pulmonary artery. Careful attention to insertion and withdrawal techniques could prevent this potentially serious complication.


Age-associated reduction in pineal beta-adrenergic receptor density is prevented by life-long food restriction in rats. At 28 months of age (old rats), male Fisher 344 rats which had been fed 40% of the ad libitum food intake since they were 6 months old, had a similar beta-adrenergic receptor density (Bmax) in their pineal gland as young, 3-month-old rats. In contrast, old rats which had been fed ad libitum for the same period had approximately 50% of the Bmax value compared to that of young rats. The beta-receptor density of cerebral cortical tissue and the beta-receptor affinity (Kd) of both the cortex and the pineal gland did not decline with age and was not affected by food restriction. The reduction in pineal beta-receptor density with age may be casually related to the concurrent age-associated decline in pineal production of melatonin.


Long-term follow-up of ICU patients.

Long-term follow-up of ICU patients. Critical care medicine programs must provide outpatient experience for their fellowship trainees. We have developed an unusual follow-up plan allowing critical care fellows to contact their patients months after their intensive care unit stay. We evaluated responses of 46 patients after a mean interval of 8.6 months since their initial intensive care unit stay. Patients were stratified by severity of disease by using the APACHE scoring system. Diagnostically, the patients represented the typical medical-surgical intensive care unit population. Patients were asked 11 questions concerning their health and socio-emotional status as it related to their hospitalization and intensive care unit stay. Our results established a practical method of providing outpatient follow-up that may fulfill residency review requirements for critical care fellowships, confirmed previously speculative ideas about ICU experiences, and suggested future research opportunities to study intensive care unit patients following discharge.


Serological survey of a captive macaque colony in China for antibodies to simian type D retroviruses. Sera from 510 macaques consisting of Macaca mulatta, Macaca assamensis, Macaca fascicularis, Macaca nemestrina, and Macaca arctoides were investigated for antibodies to simian AIDS type D retrovirus (SRV) by ELISA and Western blot with viral antigens purified from supernatants of SRV-1 infected cell cultures. Of these monkeys, 104 were seropositive by ELISA; only 23 were confirmed by Western blot. The true positive reaction to SRV was found in 15 of 463 (3.2%) M. mulatta and eight of eleven (72.7%) M. assamensis.


Detection of ornithine decarboxylase messenger RNA in human hepatocellular carcinoma by in situ hybridization. Ornithine decarboxylase (ODC) has been shown by biochemical analysis, to be important for cell proliferation and carcinogenesis in a variety of tissues, including the liver. We detected messenger RNA (mRNA) specific for the enzyme ODC in 18 patients with hepatocellular carcinoma by an in situ hybridization technique using a radiolabelled ODC probe on formalin-fixed liver specimens. Adjacent uninvolved liver tissues were used as controls. Among the adjacent uninvolved liver tissues, five showed evidence of cirrhosis. Poorly differentiated hepatocellular carcinoma has significantly higher levels of ODC mRNA than does well-differentiated hepatocellular carcinoma, which in turn has a significantly higher ODC mRNA level than adjacent uninvolved liver tissues; tissues showing evidence of cirrhosis, on the other hand, had a significantly lower ODC mRNA level than adjacent uninvolved liver tissue. This pattern of ODC gene expression in hepatocellular carcinoma is similar to the pattern of expression of other oncogenes in liver tumours. The quantitative detection of ODC mRNA in hepatocellular carcinoma by in situ hybridization may help elucidate the potential role of ODC in hepatocarcinogenesis.


Viruses in anogenital cancer.

Viruses in anogenital cancer. The association between sexual activity and cancer, first described in carcinoma of the cervix, has been expanded to include the majority of anogenital squamous epithelial carcinomas. Current evidence suggests that human papillomavirus (HPV) may be of great importance in the development of these tumours, whilst herpes simplex type 2 virus (HSV-2) and human immunodeficiency virus (HIV) may play minor roles. Certain types of HPV DNA, including types 16, 18, 31, 33 and 39 are found in most but not all anogenital cancers and pre-invasive neoplastic conditions. Viral genes E6 and E7 of HPV 16 and 18 are regularly expressed in HPV-positive tumours. In vitro, E6 and E7 genes have transforming properties which correlate with their ability to bind naturally occurring growth regulation proteins p53 and pRB. It has, however, become apparent that HPV alone does not provide the full aetiological explanation of sexually related carcinomas. The finding of latent, non-sexually-acquired HPV in a sizable proportion of the community, including children, has confounded simple theories of HPV transmission and cancer. Furthermore, in vitro experiments suggest that other factors may potentiate the effects of HPV. HSV-2 may possibly function as cofactor as it can synergize with HPV to cause transformation in vitro, and can transactivate HPV gene expression. HIV is associated with an increased rate of anogenital malignancies, particularly of the anus. Tumours in HIV-positive patients appear to have a worse prognosis, even before the onset of AIDS.


Delta-sleep-inducing peptide stimulates melatonin, 5-methoxytryptophol and serotonin secretion from perifused rat pineal glands. The pineal gland is known to synthesize numerous indolamines. Since delta-sleep-inducing peptide (DSIP, a tryptophan nonapeptide) is found in the pineal gland, its effect on the secretion of indolamines was investigated. DSIP stimulated melatonin (MEL), 5-methoxytryptophol (5-ML) and serotonin (5-HT) synthesis and release, whereas it did not affect pineal cyclic AMP levels. The stimulatory effect of DSIP on MEL secretion was dose dependent between 5 x 10(-6) and 10(-4) M, whereas the minimal effective concentration of DSIP on 5-ML secretion was higher than 10(-5) M. The effect of DSIP (10(-4) M) was compared to the effect of isoproterenol (ISO, 10(-6) M) on MEL and 5-HT release. ISO stimulated MEL secretion and concomitantly decreased 5-HT release. With regard to kinetic characteristics, the effect of DSIP (10(-4) M) on MEL release was faster and of shorter duration than the effect of ISO (10(-6) M; 2 and 4 h, respectively). At 10(-4) M, DSIP potentiated the ISO-induced increase of MEL secretion. The DSIP-stimulated release of MEL was not significantly altered when the pineal glands were treated with 10(-5) M propranolol (a beta-adrenergic antagonist), 10(-5) M prazosin (an alpha 1-adrenergic antagonist) or 10(-5) M naloxone (an opioidergic antagonist). This study demonstrates that the DSIP-induced secretion of indolamines from rat pineal glands may not be elicited through the well-known noradrenergic or opioid systems.


Role of sarcoplasmic reticulum in the contractile function of vascular smooth muscle as studied by 2,5-di-(tert-butyl)-1,4-benzohydroquinone. The effects of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), a potent selective inhibitor of hepatocyte endoplasmic reticulum Ca(2+)-ATPase, were functionally examined in rat aorta in order to assess whether tBuBHQ also acts as a Ca2+ pump inhibitor of sarcoplasmic reticulum (SR) in vascular smooth muscle. tBuBHQ elicited a slowly developing and gradually decreasing contraction which was dependent on extracellular Ca2+. We utilize the phenylephrine (PE)-induced transient contractile response in Ca(2+)-free medium as an indirect index on the status of intracellular Ca2+ store. When preparations, depleted of their PE-sensitive Ca2+ store, were allowed to replete their stores in Ca(2+)-containing medium, a sustained contraction in tBuBHQ-treated preparations was observed, whereas in untreated control preparations, readministration of Ca2+ elicited no contraction, or occasionally a weak, transient contraction. In control tissues, subsequent application of PE in Ca(2+)-free medium after Ca2+ loading resulted in full restoration of the transient contraction to PE; but such a transient contraction was not observed in the presence of tBuBHQ. These results indicated that the sequestration of Ca2+ into the PE-sensitive pool was inhibited by tBuBHQ. We also assessed effects of tBuBHQ on phentolamine-induced relaxation in PE-precontracted tissues in Ca(2+)-containing medium. A slower rate of relaxation was observed in preparations treated with tBuBHQ. In conclusion, our findings are consistent with the hypothesis that tBuBHQ acts as a SR Ca2+ pump inhibitor, interfering with effective refilling of PE-sensitive intracellular Ca2+ stores.


[Sequential quantitative scintigraphy of parotid glands with chronic inflammatory diseases]. Sequential quantitative scintigraphy of parotid glands was performed in 16 cases with recurrent parotitis in childhood, 33 with chronic obstructive parotitis, 37 with Sjögren's syndrome, 4 with sialadenosis and 30 normal controls. Uptake function was normal, but excretion was retarded in recurrent parotitis in childhood. Chronic obstructive parotitis exhibited that excretion was obstructed and the uptake and excretion function between bilateral parotids was marked different. In Sjögren's syndrome, uptake was very low and excretion was heavily delayed. Sialadenosis showed that excretion was retarded and uptake function was not definitely involved. The possible mechanism of the scintigraphical features were analyzed combined with the histopathological findings.


[125I]iodomelatonin binding sites in the chicken brain: diurnal variation and effect of melatonin injection or pinealectomy. The diurnal variation of [125I]iodomelatonin binding sites in the brain and serum melatonin levels were studied at 4-hour intervals under a 12 h:12 h light:dark cycle in 5-week-old chicks. There was a diurnal rhythm of [125I]iodomelatonin binding capacities in brain membrane preparations with the peak in the light period and the trough in the dark period. However, a diurnal variation with high levels in the dark and low levels in the light was observed in serum melatonin concentrations. The binding capacity of [125I]iodomelatonin was inversely related to the serum melatonin level. Four-week-old chicks were injected with melatonin (1 mg melatonin/kg; i.p.) twice a day (shortly after the light onset and shortly before light offset) for 3 weeks. When chickens were killed at 7 weeks, there was no diurnal rhythm of melatonin in the circulation. In addition, melatonin injection also abolished the diurnal variation of [125I]iodomelatonin binding sites in brain membrane preparations in these animals. This was achieved by decreasing the binding capacity in the light period. Pinealectomy in 2-day-old chickens increased the density of [125I]iodomelatonin binding sites in the brain membrane preparations both at midlight and middark when the chicks were later sacrificed at 6 weeks of age, although the rhythm of binding sites persisted. It is suggested that the [125I]iodomelatonin binding capacity in the chicken brain is regulated by endogenous melatonin and influenced by exogenous melatonin. In addition, the rhythmicity of [125I]iodomelatonin binding sites in the chicken brain is affected by, but not dependent on, pineal melatonin.


Priming and signal transduction in neutrophils. The priming response is a common feature for almost all agents which activate neutrophils. The priming response is associated with a number of events such as degranulation, receptor upregulation, increases in [Ca2+]i and the production of lipid second messengers. For each of these associated events there are data to suggest that priming can also occur in their absence. These contradictions suggest that either the true mechanism for priming has not been found or that there are multiple pathways by which the primed state can be reached. The latter is more likely to be the case.


Recurrent genital infection in the guinea pig: differences between herpes simplex types 1 and 2. Recurrence rates of genital infections are significantly higher for herpes simplex virus (HSV) type 2 than HSV type 1. Reasons for this difference are not known. In this report, multiple strains of HSV-1 and HSV-2 were evaluated in the guinea-pig model. HSV-2 strains showed significantly higher genital lesion recurrence than HSV-1, including HSV-1 McKrae strain which is highly recurrent in ocular infections. HSV-2 strains were also associated with more frequent asymptomatic vaginal virus shedding. Further study showed that HSV-1 strains replicated as well as HSV-2 in both the genital tract and the nervous system during acute infection. In addition, no difference was detected between HSV-1 and HSV-2 in nervous system latency. Thus, a number of possible explanations for the observed difference in genital herpes recurrence rates were examined and excluded.


Rapid detection of waterborne viruses using the polymerase chain reaction and a gene probe. We describe a membrane-filter-based urea-arginine phosphate buffer method for concentrating waterborne viruses from large volumes of water to microlitre volumes, and their subsequent detection by the polymerase chain reaction (PCR). The detection step involves the extraction of RNA, synthesis of complementary DNA, amplification by PCR of target DNA with specific primers, and confirmation through nucleic acid hybridization with a radiolabelled oligonucleotide probe. The PCR technique detected the presence of enteroviruses in spiked as well as in contaminated water samples. The technique is sensitive and detects as few as 120 waterborne viral particles. PCR is simple, rapid, sensitive, specific and adaptable for water quality surveillance in less developed countries.


The heat-induced hsp 70 promoter activity is negatively regulated by serine phosphatases: evidence from the effects of okadaic acid. We examined the effects of okadaic acid (OA), a potent and specific inhibitor of serine phosphatases 2A and 1, on the transient expression of an hsp 70 promoter-reporter gene construct in IMR-90 human diploid lung fibroblasts. We showed that OA markedly potentiated the heat-induced but not the basal expression of pHBCAT, a full-length human hsp-70-promoter-driven CAT gene construct. This effect of OA was dose and time dependent and promoter specific. Importantly, the potentiating effects of OA appeared to be independent of the binding of the activated heat shock transcription factor (HSTF) to its consensus DNA sequence, the heat shock element (HSE). Thus, OA had no effect on the HSTF DNA-binding activity as measured by mobility shift assay, and mutation of the HSE sequence did not obliterate the stimulatory effects of OA on reporter gene expression under a heat shock condition, although heat shock by itself was without effect. Analysis of the status of phosphorylation of the largest subunit of RNA polymerase II provided evidence that this effect of OA is attributable, at least in part, to the increased phosphorylation of RNA polymerase II. These results provided evidence that the heat-induced hsp 70 promoter activity is negatively regulated by serine phosphatases. We propose that the heat-induced transcriptional activation of hsps is associated with phosphorylation of component(s) of the transcription complex; one of the likely candidates being the transcriptionally engaged RNA polymerase II. OA, by inhibiting phosphatase 2A and 1 activity, enhanced this phosphorylation and potentiated the transcriptional activation of hsps.


Prevalence of antibody to Epstein-Barr virus DNase in children. Antibodies to Epstein-Barr-virus-specific DNase in children under 15 years old from Taipei, Taiwan were determined by an enzyme neutralization test. Serum was taken as positive for the anti-DNase antibody when 1 ml of serum could neutralize > or = 2 units of the DNase activity. Among the 1,292 sera tested, 5.6% of the children were shown to have anti-EBV DNase antibodies, a result similar to that for adults. Maternal antibodies against the EBV DNase were found to decrease very rapidly 2 months after the child's birth, and new antibody appeared upon natural EBV infection.


A study of nerve conduction velocity in patients on diphenylhydantoin therapy. Peripheral nerve conduction studies were performed in 30 epileptics, treated with DPH and results were compared with age and sex matched controls. There was significant reduction in the amplitude of sensory nerve action potential of median (26.65 +/- 14.71 mu v) and superficial radial nerve (25.65 +/- 10.08 mu v) (p < 0.001) in DPH treated group as compared to controls, (median nerve 42.64 +/- 15.93 uv and superficial radial nerve 40.72 +/- 24.74 mu v). The results suggest that DPH causes a subclinical distal axonal neuropathy in therapeutic dosage.


Corticosteroid receptor plasticity in the central nervous system of various rat models. The action of corticosteroids in the central nervous system (CNS) is mediated by two distinct corticosteroid receptors: the mineralocorticoid and glucocorticoid receptors (MR and GR respectively). Using an established in vitro binding assay system, MR and GR binding parameters were determined in the hippocampal, hypothalamic and pituitary cytosol of various rat models. In the (pharmaco-)genetically selected rat lines, the apomorphine susceptible (APO-SUS) rats showed a significant increase in the hippocampal and pituitary MR binding capacities (but not affinity) compared to those in the apomorphine-unsusceptible (APO-UNSUS) rats. In immunologically-altered Lewis (LEW/N) rats and in spontaneously hypertensive rats (SHR), increased hippocampal MR capacity (but not affinity) and hypothalamic MR capacity were observed compared to their respective control, Wistar (WIST) and Wistar Kyoto (WKY) rats. In addition, compared to WKY rats, SHR rats also showed a much greater pituitary but lesser hypothalamic GR binding capacity. In rats subjected to alteration in environmental conditions, the long-term effects of a short inescapable stress resulted in a significant increase in both hippocampal MR and GR while the pituitary and hypothalamic MR and GR do not differ in the stress and control groups. In rats subjected to a defeat test, a decrease in hippocampal MR and GR was observed 3 weeks (but not 1 week) later.


Molecular analysis of the t(15;17) translocation in acute promyelocytic leukaemia. APL (FAB M3) is a unique type of myeloid leukaemia characterized by specific clinical, morphological, cytogenetic and molecular features. An early and accurate diagnosis is necessary to initiate therapy and treat the life-threatening coagulopathy caused by release of procoagulants from the abundant promyelocytic granules. Cytogenetically the disease is characterized by a reciprocal translocation between the long arms of chromosomes 15 and 17, t(15;17)(q21;q22), which is seen in almost every patient with APL but in no other form of malignancy. The presence of this translocation, often as the only karyotypic change, suggests that potentially leukaemogenic sequences are located at the breakpoints and are activated by rearrangement. The recent cloning of the breakpoints by three groups has demonstrated that the retinoic acid receptor alpha gene (RARA) on chromosome 17 is fused to a previously undescribed transcription factor gene, PML, on chromosome 15. The DNA-binding motifs of both the RARA and PML proteins, together with the ligand-binding domain of RARA, are combined in a single fusion protein which may dysregulate either retinoic acid or PML-sensitive pathways. Identification of these dysregulated target genes has become the next molecular goal for research on APL. Intriguingly, some APLs not only express the PML-RARA fusion protein but also the reciprocal RARA-PML fusion protein, although the contribution of this product is unclear. The PML-RARA chimaeric protein is presumably the target during the striking differentiation therapy achieved with all-trans retinoic acid. This therapy induces the malignant promyelocytes to mature and die, rather than continue proliferating. Moreover, it represents the first direct connection between a genetic defect and clinical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Myeloid malignancies and chromosome 5 deletions. Deletions of chromosome 5 were initially reported as a consistently occurring chromosomal abnormality in 5q- syndrome. They have since been recognized to occur in other myeloid malignancies such as therapy-related leukaemia and de novo AML as well. The variability of the deletions, and the heterogeneity of the clinical syndromes, have made it difficult to describe a single clinical-molecular entity such as we see with chromosomal translocations described elsewhere in this volume. Translocations in leukaemogenesis often have a dominant effect leading to activation of oncogenes or the production of a modified protein. Consistently occurring chromosomal deletions in human tumours, however, have been regarded as evidence that the affected regions contain tumour suppressor genes. Loss of function of these tumour suppressor genes or 'recessive oncogenes' leads to cancer. Deletions in the long arm of chromosome 5 in myeloid malignancies are thought to signal the existence of a recessive oncogene on 5q, which is homozygously inactivated in these malignancies. Here we describe the clinical and molecular features of the diseases associated with deletions of chromosome 5 in an attempt to propose a unified approach to identifying the genes on 5q which are involved in leukaemogenesis. It is likely that the clinical heterogeneity of these disorders will not be understood until the relevant genes are cloned and their role in the initiation or progression of leukaemia is known.


Receptor changes and LTP: an analysis using aniracetam, a drug that reversibly modifies glutamate (AMPA) receptors. The hypothesis that long-term potentiation (LTP) involves receptor modifications was tested with aniracetam, a nootropic drug that selectively increases currents mediated by the AMPA subclass of glutamate receptors. Aniracetam had different effects on the waveform of synaptic potentials in hippocampus before and after induction of LTP: (1) the drug caused a slight reduction (or delay) of the initial segment of the response after LTP; and (2) the facilitatory effects of aniracetam occurred at a later time point in the response after LTP than before. The interactions between LTP and aniracetam were still present when synaptic responses were greatly reduced by partial blockade of postsynaptic receptors and were not reproduced by increasing release or the number of stimulated synapses. A mathematical treatment of synaptic currents produced the following results: (1) if aniracetam facilitates AMPA receptor currents simply by reducing desensitization, then its complex interaction with LTP emerges when potentiation changes the kinetic and conductance properties of receptor channels; (2) if aniracetam also significantly increases conductance, then the experimental data can be reproduced by modeling LTP as an increase in channel conductance alone.


Isoproterenol increases the phosphorylation of the synapsins and increases synaptic transmission in dentate gyrus, but not in area CA1, of the hippocampus. Previous studies have shown that either norepinephrine (NE) or isoproterenol (ISO) enhances the slope of the field excitatory postsynaptic potential (EPSP) in the dentate gyrus of the rat hippocampal formation. In contrast, NE and ISO cause no increase in excitatory transmission in area CA1 of the hippocampus. The molecular mechanism underlying this brain region-specific increase in synaptic transmission is not known. The phosphorylation of synapsin I and synapsin II, two homologous presynaptic vesicle-associated proteins, is thought to promote neurotransmitter release. The authors have observed previously NE- and ISO-enhanced phosphorylation of synapsins I and II in the dentate gyrus. The purpose of this study was to determine whether ISO-stimulated phosphorylation also occurs in the CA1, where ISO has no effect on excitatory neurotransmission. These studies were correlated with electrophysiological studies in in vitro hippocampal slices. Superfusion of slices with ISO resulted in an increase in EPSP slope in the dentate but not in area CA1. The enhanced dentate EPSP returned to baseline levels within 30 minutes of washout of the drug. Isoproterenol produced corresponding increases in the phosphorylation of the synapsins in dentate slices but had no effect on these proteins in CA1 slices. Moreover, in dentate slices exposed to a 30-minute wash following incubation with ISO, phosphorylation of the synapsins returned to control levels. This close temporal and brain regional correlation between ISO stimulation of both synapsin phosphorylation and synaptic transmission suggests that the synapsin proteins may play a role in the synaptic potentiation produced by ISO in the dentate.


[The occurrence of rotaviruses and adenoviruses in children up to 11 years old without diarrheal symptomatology in Goiânia, Goiás]. Three hundred and eighty-five children without a diagnosis of diarrhoeal illness had faecal specimens collected in order to detect rotavirus infection. The survey was conducted in Goiânia city--central Brazil and the children aged 0-11 years old were recruited (268 in day care centers and 117 from a local outpatient clinic--Hospital Lucio Rebelo). Detection of rotavirus was done by polyacrylamide gel electrophoresis (PAGE-SDS), and 89 specimens were also analyzed by commercial enzyme immunoassays for rotavirus and adenovirus (EIARA). Rotaviruses and adenoviruses were only detected among the children attending the outpatient clinic. Prevalence rates of rotavirus and adenovirus excretion were of 1.7% and 1.6%, respectively. Both viruses were found among children from 1 to 2 years old.


Spontaneous recovery of deficits in spatial memory and cholinergic potentiation of NMDA in CA1 neurons during chronic lithium treatment. The therapeutic action of lithium in affective disorders is still unclear. One effect of lithium is to deplete membrane inositol and consequently to exhaust the phosphoinositide (PI) pathway. Under chronic lithium treatment, rats showed persistent performance deficits in an active avoidance task and in a visually cued maze. The same treatment, however, resulted in only a transient deficit in the performance of rats in a spatial memory task. Lithium treatment caused a similarly transient deficit in the ability of acetylcholine to potentiate responses to N-methyl-D-aspartate (NMDA) in neurons of the hippocampal slice. The authors propose that the development of compensatory mechanisms may account for the lack of severe memory impairments during lithium treatment. It is suggested that the effects of lithium on the PI pathway are not sufficient to explain the behavioral consequences of chronic lithium treatment.


Protective effects of thiol containing chelating agents against liver injury induced by hexavalent chromium in mice. The effects of the chelating agents, L-cysteine ethyl ester (LCEE), L-cysteine methyl ester (LCME), N-acetyl-L-(+)-cysteine (NAC), 2,3-dimercapto-1-propanesulfonic acid (DMPS), N-(2-mercaptopropionyl)-glycine (MPG), and 2,3-dimercaptosuccinic acid (DMSA), on the distribution, excretion and hepatotoxicity of ip injected hexavalent chromium were studied in male mice. The chelating agents (500 mg/kg) were injected iv as single doses given immediately or 30 min after potassium dichromate (20 mg Cr/kg) as hexavalent chromium was administered. When the chelating agents were injected immediately after the metal compound was administered, LCEE, LCME, NAC, DMPS, and MPG reduced the chromium contents in the liver and kidney, and facilitated the urinary excretion of chromium. The liver injury induced by chromium, which was evaluated by serum ornithine carbamyl transferase (OCT) activity, was prevented significantly by LCEE, LCME, DMPS, and MPG. On the other hand, when these chelating agents were injected at 30 min after the chromium administration, only DMSA could prevent the liver injury induced by the metal, and decreased the chromium contents in the liver. However, when DMSA was given at 3 hr after the metal administration, there was no therapeutic effect on them. These results suggest that the chelating agents tested may be useful in the treatment of intoxications due to hexavalent chromium, but there is the difference in the therapeutic effects of the chelating agents owing to the time intervals after the administration of the metal.


Depression of early protection against influenza virus infection by cyclophosphamide and its restoration by protein-bound polysaccharide. Relationship between depression of early protection against influenza virus infection and the decrease in the number of peripheral polymorphonuclear leukocytes in cyclophosphamide-treated mice was investigated using protein-bound polysaccharide (PSK), which had been shown to exert a potent restorative effect on leukocytopenia in immunocompromised hosts. Following intranasal inoculation with influenza virus (1.5 x 10(3) PFU) into untreated mice, the pulmonary virus titer progressively increased during 3 days and decreased gradually from the day 7 after infection. The treatment of mice with cyclophosphamide (150 mg/kg) 2 days before infection markedly enhanced the pulmonary virus multiplication from the early phase of infection, and the higher virus titer was maintained thereafter. When mice were given cyclophosphamide after PSK-treatment, virus titers from the early to late phases of infection were lower than those in untreated mice.


46,XX pure gonadal dysgenesis with growth hormone deficiency and impaired 3 beta-hydroxysteroid dehydrogenase activity. Patients with 46,XX pure gonadal dysgenesis generally are of normal stature and have less than usual amounts of pubic and axillary hair. We report on a patient who presented at age 11.9 years with short stature, absence of breast development, and excessive pubic hair. Her karyotype in leukocytes, fibroblasts, and streak gonad was 46,XX. The patient was diagnosed as having growth hormone deficiency. Elevated ACTH stimulated levels of 17-hydroxypregnenolone and dehydroepiandrosterone and elevated ACTH stimulated ratio of 17-hydroxypregnenolone to 17-hydroxyprogesterone suggested inadequate adrenal 3 beta-hydroxysteroid dehydrogenase activity. Treatment with growth hormone resulted in improvement in growth velocity and replacement with estrogen in feminization. We suggest that the finding of short stature in patients with 46,XX pure gonadal dysgenesis should not be attributed to the syndrome, but rather requires investigation for possible growth hormone deficiency. The poor growth of our patient prior to growth hormone replacement implies that dehydroepiandrosterone, unlike testosterone and estrogen, is ineffective in promoting linear growth in the absence of adequate growth hormone.


45,X/46,X,+r(X) can have a distinct phenotype different from Ullrich-Turner syndrome. We present a patient with 45,X/46,X,+r(X) mosaicism and lack of inactivation of either the normal or the ring X in the 46,X,+r(X) cells. The patient has mental retardation, syndactyly, minor facial anomalies, and a congenital heart defect. Although most patients with 45,X/46,X,+r(X) have the Ullrich-Turner syndrome, 2 previously described patients with this karyotype also had a distinct phenotype consisting of severe mental retardation, syndactyly, and abnormal face. The unusually severe phenotype in these patients was thought to be due to lack of X-inactivation of the ring X chromosome. The findings in our patient support this hypothesis.


[Cytomegalic infection: importance of congenital cytomegalovirus infection in the genesis of cerebral palsy]. In developed countries the congenital cytomegalovirus inclusion disease is considered to be nowadays an important problem of public health due to the great number of mental deficiency and deafness caused by it. In Brazil, publications related to the subject are rare, and more specifically they treat about pathologic and epidemiological aspects of the infection. In this study it is intended to show in our country the importance of the infection in the genesis of chronic encephalopathies. Emphasis is given to the clinical and serologic aspects.


Propylthiouracil and peripheral neuropathy. Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.


Electrophysiologic studies in leprosy.

Electrophysiologic studies in leprosy. The author reviews the literature on electromyography and nerve conduction velocity studies in leprosy. It is concluded that these studies can be helpful in the early diagnosis of neural involvement, in the elucidation of pathophysiological mechanisms, and in the follow-up of patients under medical and/or surgical treatment.


[The detection of human papillomaviruses in histological preparations by using dot-blot hybridization]. The 56 tissue samples were obtained from female patients with anogenital tumors, benign or malign, subsequently confirmed through pathomorphological analysis. The investigations were aimed at the discovering of HPV presence using hybridization techniques with biotinylated molecular probes and monitorisation through enzymatic reaction. The presence of ADN types 11, 16 and 18 was detected on about 52% of all the cases; the ADN HPV incidence was 57% among the patients with a neoplasm and/or cervix uteri papillomatosis diagnosis.


[Early anti-HPV 16 protein antibodies in patients with anogenital tumors]. A study was worked out in female patients with anogenital tumors and in apparently healthy women, aimed at the detection of antibodies against E4 and E7 HPV 16 proteins. As regards the detection of HPV 16 infection, the DNA hybridization and Western-blot results were in good agreement. The HPV 16 infection was detected in a relatively high number of the patients (17 out of 24) and of the apparently healthy women using Western blot.


Induction of chemiluminescent emission in polymorphonuclear leucocytes stimulated by Sendai virus. Sendai virus (SV) stimulates in vitro the chemiluminescent emission (CHL) of human polymorphonuclear leucocytes (LPMN). The kinetics of CHL produced by LPMN depends on the structure of stimulus, the intensity being dependent of the immunological status of the subject. CHL induced by Sendai virus is similar to that given by phorbol-myristate (PMA) as regards the induction of an early maximum. To obtain CHL significant emission, an optimum ratio between LPM concentration and Sendai virus dilution is required. The maximum effect is obtained in a large scale of dilution of Sendai virus ranging from 6,000 to 16,000 uHA.


[Antibody titers against the hepatitis A virus in a healthy population from an urban health area]. To assess the level of immunity in a healthy population to the hepatitis A virus (HAV), according to age groups and in an urban health area. Transversal random prospective study of a sample of the population found by letters. SITE. Primary Care Centre covering the population of an urban health area in Valladolid. Random sample of 726 people with an adjustment as to sex and age according to the area's average, in line with the full census of the above area. The sample was 95% trustworthy, with a 3% margin of error. People with serious illness at the time of the study were excluded. We carried out a social-health count. We established the anti-HAV titer after its detection by enzyme immunoanalysis (HAVAB EIA Abbott); the titers were inferred from the absorbances relating then to that of a a "pool" of serums with very high titers. 69.9% (standardised rate) gave positive. The highest titers were presented in people between 31 and 50 (29.7 +/- 47.0), with significant differences both for lower (17.0 +/- 15.7) and higher (15.7 +/- 19.8) age groups (p. 0.001 for both). The highest anti-HAV titers corresponded to people in the middle age-group, with a subsequent dropping-off. This could suggest a greater susceptibility to HAV infection in the older person.


[The mechanisms of the antiherpetic action of aqueous propolis extracts. I. The antioxidant action on human fibroblast cultures]. A redox state modulation model was worked out in human fibroblast cultures treated with oxidation stress inducing agents and a redox agent, virtually protecting cell against the stress. Quantification of the global redox changes in fibroblasts was done using the hemoglobin electronic spectrum, in the presence and in the absence of H2O2.


Adreno-cortical reserve in pulmonary tuberculosis. Serum cortisol in response to ACTH was assessed in 28 patients with moderately severe to far advanced pulmonary tuberculosis. Ten healthy individuals served as controls. Whereas the basal values were comparable in the two groups the mean delta peak, mean and area under the response curve were significantly lower in the tubercular patients (p < 0.05 to 0.001). Six patients had negligible cortisol response to ACTH stimulation while five others exhibited an inadequate response (rise between 200-300 nmol/L0. None of the subjects had any clinical evidence of adrenocortical insufficiency. The data thus revealed a functional impairment of adrenal cortical reserve in patients of pulmonary tuberculosis.


Antiviral activity of some copper complexes of symmetrical triazines. Copper complexes of hydrazones derived from symmetrical triazines inhibit the multiplication of three different types of viruses (Sendai, HSV and VSV) showing as well a scavenger activity on O2- radicals. The results emphasize the antiviral activity of these complexes which have at the same time a O2- radical scavenger activity.


Ultrasonographic patterns of hepatobiliary mass lesions. The study deals with an analysis of ultrasonographic (USG) patterns in 100 consecutive patients with hepatobiliary mass lesions. Amoebic liver abscess, carcinoma (CA) gall bladder and secondaries in liver comprised nearly 70% of cases. USG appearances in liver abscess, hepatoma, secondaries in liver and CA gall bladder were variable, but were characteristic in hydatid disease and congenital polycystic disease. Two patients with cholangiocarcinoma revealed dilated biliary channels with an intraluminal mass in common bile duct.


An efficacy study of itraconazole in the treatment of Penicillium marneffei infection. to evaluate the efficacy and safety of itraconazole in treating P. marneffei infection. Ten patients with previously untreated P. marneffei infection were given oral itraconazole at a dose of 200 mg twice a day for 2 months, followed by a dose of 100 mg once a day for 1 month. Efficacy was determined by the clinical and microbiological cure. All but one patient were seropositive for human immunodeficiency virus (HIV). Two patients died during therapy. Clinical improvement was evident in 8 patients. In 7 of these, the mean duration for becoming culture negative was 57 days. Five patients presented with relapse of P. marneffei infection within four months after completion of treatment. Itraconazole was shown to be effective in the initial treatment of P. marneffei infection. Relapse after treatment is common and long-term suppressive therapy is recommended.


Aminoglycoside antibiotics alter the electrogenic transport properties of cultured human proximal tubule cells. Monolayers of human proximal tubule (HPT) cells, when grown on permeable supports and mounted in Ussing chambers, spontaneously display a transepithelial potential difference (PD) and short-circuit current (Isc). These electrical parameters were used in the present study to determine if aminoglycoside exposure altered electrogenic sodium transport by HPT cells. The results of this determination demonstrated that exposure to gentamicin, at levels below that producing cell necrosis, caused a marked reduction in Isc and that this reduction followed the known in vivo nephrotoxicities of the aminoglycosides streptomycin, gentamicin, and neomycin. It was concluded through a similar analysis on a total of 14 isolates of HPT cells that the aminoglycosides repeatably reduced the electrogenic sodium transport of HPT cells. It was further determined that this alteration in electrogenic transport by gentamicin was mediated through exposure of the drug to the basolateral cell surface and that apical exposure had little effect. Evidence was obtained against the involvement of Na+, K(+)-ATPase, adenosine 3',5'-cyclic monophosphate, and sodium-coupled substrate transport in this alteration in electrogenic transport by the aminoglycosides. The basolaterally located Na+: CO3(-2):HCO3(-1) symporter is a possible site for aminoglycoside-induced nephrotoxicity.


The effect of ethyl alcohol on peroxidation processes and activity of antioxidant enzymes in rat's gastric mucosa. The severity of damage to gastric mucosa and the levels of malonyl dialdehyde (MDA), hydroperoxides, conjugated dienes (C.D.) as well as the activity of catalase (EC 1.11.1.6), peroxidase (EC 1.11.1.7), glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1.) in rat's gastric mucosa were assessed 2 hours after the oral administration of 50% ethyl alcohol by means of a stainless steel tube. It was found that 50% ethanol administered per os caused numerous ulcerous changes in gastric mucosa, increased the levels of MDA, hydroperoxides, both isoenzymes of superoxide dismutase (Cu, Zn SOD and Mn SOD), glutathione peroxidase and glutathione reductase. The interpretation of the phenomenon was presented, emphasizing the protective role of antioxidant enzymes counteracting the formation of ulcers in gastric mucosa.


Level of cortisol and reactivity of adrenal cortex to exogenous ACTH at neonatal period in calves. The studies were carried out on calves from 1st to 21st day of life. Cortisol level and reactivity of adrenal cortex to exogenous ACTH were analysed. The highest level of cortisol in blood was observed in first days of life in the calves. Then the level became considerably decreased. In the experimental group two subgroups differing in cortisol level were distinguished. High or low level occurred on the first day and the difference kept over two weeks of their life. Adrenal cortex just on the day of birth showed full functional maturity of molecular receptors binding ACTH.


Detection of cytomegalovirus in urine of HIV-infected patients by DNA-DNA hybridization comparison with virus isolation, immunofluorescence and immunoperoxidase. Immunofluorescence and immunoperoxidase test directed against early viral antigens, and DNA-DNA hybridization were compared with viral isolation for their abilities to detect Cytomegalovirus (CMV) in the urine of 89 HIV infected patients. From the 100 urine samples collected, 70 were found positive by at least one method. Considering viral isolation as the "gold standard" technique, immunofluorescence and immunoperoxidase had a sensitivity of 92.3% and 88% respectively, with a specificity in both cases of 95%. DNA-DNA hybridization showed a sensitivity of 90% but with lower (60%) specificity. All of the three assays were effective in detecting CMV from urine and the technical advantage of each is discussed.


[Changes in activity of G-6-pase, APase, and gamma-GTPase in liver and blood serum of rats exposed to nuarimol and NDEA]. The effect of simultaneous administration of N-diethylnitrosamine (NDEA) and Nuarimol on the activity of gamma-GTPase, G-6-Pase ans APase in the liver and serum of Wistar rats was investigated in the 2-weeks experiment. The two-stage hepato-cancerogenesis model was used with NDEA as initiating agent. The possible promoting potential of Nuarimol (DDT analogue) was checked in this experiment. gamma-GTPase and G-6-Pase activities were measured by biochemical and histochemical methods and AP-ase activity was measured by a biochemical method only. The occurrence of gamma-GTPase positive foci found by histochemical methods was partly confirmed by colorimetric methods. This suggest the need for further examination of this enzyme in conditions of prolonged exposure to Nuarimol.


[Dietary fiber in the dietetic therapy of diabetes mellitus. Experimental data with purified glucomannans]. In the last years the use of alimentary fibres in dietetic management of diabetic patients increased. The aim of this work was to evaluate, in type 2 diabetic subjects, the glycaemic and insulinemic increments after a standard breakfast with glucomannanos enriched biscuits and with common slices of toast containing the same amounts of carbohydrates and calories. The basal serum values of glucose and C-peptide were similar in the two days of the test. The mean increments of glucose and C-peptide were significantly higher (p < 0.001) after slices of toast than after glucomannanos enriched biscuits. In conclusion our results show a reduction in glycaemic increments after breakfast with glucomannanos-biscuits. The decreased insulin secretion and the reduction of insulin need can longer preserve the functional reserve of beta-cells.


Antagonism by potassium of the inhibition of (Na(+)+K+) ATPase produced by an endogenous digitalis-like compound extracted from mammalian heart. The antagonism by potassium of (Na(+)+K+)ATPase inhibition was analyzed in order to further study the presence of endogenous digitalis-like activity in mammalian heart. Digoxin and a partially purified extract prepared from guinea pig cardiac tissue inhibited (Na(+)+K+)ATPase, also obtained from guinea pig heart, in a dose-dependent manner in agreement with Michaelis-Menten kinetics. The effects of both inhibitors were antagonized by increasing the KCl concentration from 0.5 to 5 mM. Hunter-Downs plots were linear, suggesting that the interaction between (Na(+)+K+)ATPase and either digoxin or the extract could be considered as competitive. Ks estimated for KCl from these plots was similar to the K0.5 value obtained by activating the enzyme with KCl, and thus suggesting that both inhibitors, digoxin and the extract, were acting on (Na(+)+K+)ATPase. Digoxin and the extract were able to inhibit [3H]ouabain specific binding to the enzyme in a dose-dependent manner in agreement with a competitive interaction. Ki values estimated from binding experiments were similar to those calculated from Hunter-Downs plots. Data strongly suggest the presence in guinea pig heart of an endogenous compound which is able to inhibit (Na(+)+K+)ATPase solely by binding to the digitalis receptors.


Lack of in vitro interference between SA-11 rotavirus and attenuated poliovirus type 1. To determine if rotavirus interferes with the multiplication of poliovirus, and hence the efficiency of the polio vaccine, the effect of timing and concentration of Simian rotavirus (SSA-11) on polio-1 infection in MA-104 cells was studied in vitro by evaluating the cytopathic effect, the reduction of the infectivity titers and the visualization of viral particles by electron microscopy. We found that poliovirus 1 was able to replicate when the challenge dose was administered within the first 8 h following SA-11 infection and with titers ten times lower than those of rotavirus. Hence, non-interference effect was observed in this in vitro model.


Opsonic capacity of a hyperimmune serum against outer membrane proteins of Klebsiella pneumoniae. The opsonic capacity of a hyperimmune rabbit serum against a porin-rich outer membrane protein preparation of a strain of K. pneumoniae was evaluated. By immunoblot, the antiserum recognized mainly the porins from an outer membrane protein preparation. Using an ELISA, the titer of anti-porin antibodies was determined. Through a chemiluminescence assay, the increase in the respiratory burst of murine hyperimmune serum was recorded. These data correlate with the results of the microbicidal assays and with the electron microscopy preparations obtained where a great number of bacteria were seen within the macrophages. The in vitro data show that there is a greater bacterial killing when the macrophage is infected with bacteria opsonized with the hyperimmune serum.


The seroepidemiology of hepatitis A and B in a Japanese town. Sera collected from 1,118 healthy children and adults aged between four years and 90 years during the period 1989 to 1990, were tested for serological markers of hepatitis A virus (HAV) [antibody to HAV (anti-HAV)] and hepatitis B virus (HBV) [hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBsAb)]. The overall prevalence rates of anti-HAV, HBsAg, and anti-HBV were 20.2%, 0.36%, and 5.1%, respectively. No body was found to be positive for anti-HAV below 30 years of age but more than 70% of the adults aged 50 years or over were positive for anti-HAV. The level of exposure of HAV infection is declining in Japan and paradoxically at the same time a vast majority of people are becoming susceptible to more severe illness. The fall in prevalence of HBsAg possibly represents the positive impact of ongoing vaccination programs and other preventive measures against HBV.


Digitalis-like compounds in animal tissues. The Na+, K+ activated adenosine triphosphatase is present in the membrane of eukaryotic cells and represents a major pathway for Na+ and K+ transport across the plasma membrane. Cardiac glycosides such as ouabain or digoxin suppress this enzyme activity by binding to a specific receptor on the membrane. Studies conducted in this and other laboratories have proven the existence of digitalis-like compounds in animal tissues which may serve as in vivo regulators of the Na+, K(+)-pump activity. This review summarizes the attempts to identify these compounds from animal tissues and examines the potential physiological role of some of the identified compounds.


Multiparametric evaluation of brain functions in the Mongolian gerbil in vivo. We have developed the multiprobe assembly (MPA) by which metabolic, ionic and electrical activities can be monitored from the surface of the brain. In the present study we included optical fibers for the monitoring of intracapillary hemoglobin oxygenation by use of the Erlangen Microlight Guide Spectrophotometer (EMPHO-I) from the surface of the gerbil brain. The newly developed MPA provides simultaneous information about oxygen delivery (oxydeoxy Hb), tissue pO2 level, as well as the intracellular oxygen balance (intramitochondrial redox state). The ionic homeostasis was evaluated by monitoring extracellular K+ and Ca2+ activities reflecting the permeability changes of cation channels as well as the activities of Na+,K(+)-ATPase and other ion linked transport processes. The electrical activities were monitored by a bipolar electrocortical surface probe and DC steady potential. The subjects of the present study were Mongolian gerbils (Meriones unguiculatus) anesthetized and operated according to our routine techniques. After 30 min of recovery from the operation each gerbil was exposed to a short anoxia, graded hypoxia, ischemia as well as spreading depression. The results can be summarized as follows: 1. A clear correlation was recorded between the changes in oxydeoxy Hb spectra, tissue pO2 level and oxidation-reduction state of intramitochondrial NADH under oxygen deficiency situations (hypoxia, ischemia). 2. Blood volume changes under various perturbations monitored by various probes (366 reflectance and EMPHO-I) correlated very well with each other. 3. The degree of inhibition of Na+,K(+)-ATPase induced by oxygen deficiency could be interpreted by changes in extracellular levels of K+ measured by the surface mini-electrode. 4. Brain stimulation induced by spreading depression mechanism led to transient changes in ionic homeostasis and increase in energy requirements. The major HbO2 response was an increase in oxygenation due to the large CBF increase as monitored by the laser Doppler flowmeter. 5. Changes in oxy-deoxy Hb under fast scanning of 500-600 nm during 2-3 seconds of bilateral carotid arterial occlusion provided an indirect index for tissue O2 consumption.


[Disorders of circadian rhythms in depression]. The authors make a synthesis of studies about circadian rhythms in depression and of hypothesis to explain them. They successively study trials on the phases, on the average levels, on the amplitude of rhythms. They conclude the most significant troubles are, shortening of latency on paradoxical sleep for phases, slump of melatonin levels, blunded amplitude of every parameter. Among possible explanations, they present and discuss a trouble of oscillators, a decrease of sensitivity to external synchronizers and a trouble in rhythm coupling.


[Role of neuropeptides in the pathogenesis of pain syndrome in autonomic and sensory polyneuropathy of occupational etiology and their role in the therapeutic action of laser acupuncture]. Biochemical studies of opiate system in patients with occupational diseases showed the role of the central pain regulating system inducing the pain syndrome in autonomic and sensory polyneuropathy caused by occupational factors. Increased production of the pain-reducing endogenic neuropeptides such as endorphin and leucine enkephalin was found one of the He-Ne laser acting principles which restore the pain adaptation in human. A repeated course of laser therapy would normalize the content of both neuropeptides. Blood levels of neuropeptides may serve for evaluating the pain syndrome and estimating of laser therapy effects.


Transient expression of RSVCAT in transgenic zebrafish made by electroporation. We report the fish use of an exponential decay electroporation system to introduce foreign DNA into fertilized zebrafish embryos. The plasmid RSVCAT (Rous sarcoma viral promoter (RSV) upstream from the chloramphenicol acetyltransferase gene (CAT)) was linearized and introduced into fertile zebrafish embryos by electroporation no later than the four-cell stage. Conditions for the procedure were empirically derived, and 68% of the treated animals survived through hatching to at least 6 days after fertilization and well beyond. Dot-blot analysis on DNA extracted from individual hatching fry demonstrated that 65% of the animals tested carried the foreign construct. Enzyme assays on the soluble proteins of treated animals were positive for chloramphenicol acetyltransferase activity. These data demonstrate that the foreign construct was being transiently expressed in the developing tissues of the embryo. The simplicity of this technique will greatly enhance the ability to analyze gene promoter regulation in vivo in transgenic zebrafish. The ability of the electroporated DNA to integrate into the host genome and to generate stable lines of transgenic fish is discussed.


Enhancement of effector cell activities in mice bearing syngeneic plasmacytoma X5563 by a biological response modifier, PSK. We investigated the effect of PSK, a protein-bound polysaccharide obtained from Coriolus versicolor of basidiomycetes, on antitumor immunity in tumor-bearing mice. PSK prolonged significantly the life span of C3H/He mice bearing syngeneic plasmacytoma X5563 in a schedule- and dose-dependent manner. PSK was most effective when administered at 100 mg/kg every other day ten times starting from the day after tumor inoculation. The administration of PSK enhanced significantly the cytostatic activity of peritoneal exudate plastic-adherent cells and the cytolytic activity of spleen cells after in vitro incubation with mitomycin C-treated tumor cells. In addition, PSK restored the cytokine-producing capacity of spleen cells suppressed in tumor-bearing mice after in vitro incubation with mitogen. Sera from tumor-bearing mice suppressed the activity of such effector cells as well as the interleukin 2-producing capacity of spleen cells, but sera from PSK-treated tumor-bearing mice prevented this suppression. These results suggest that PSK enhances antitumor immunity by reducing immunosuppressive activity of serum from tumor-bearing mice.


Analysis of heterologous and homologous promoters and enhancers in vitro and in vivo by gene transfer into Japanese medaka (Oryzias latipes) Xiphophorus. Efficient expression systems are required for analysis of gene regulation and function in teleost fish. To develop such systems, a number of inducible or constitutive promoter and enhancer sequences of fish or higher vertebrate origin were tested for activity in a variety of fish cell lines and in embryos of the Japanese medaka fish (Oryzias latipes) and Xiphophorus. The activity of the different promoter-enhancer combinations were quantitated. Considerable differences were found for some constructs if tested in vitro or in vivo. Fro the data obtained, a set of expression vectors for basic research as well as for aquaculture purposes were established.


Prospective comparison of blood and peritoneal lymphocytes from continuous ambulatory peritoneal dialysis patients. Although a few studies have analyzed the characteristics of peritoneal lymphocytes from continuous ambulatory peritoneal dialysis (CAPD) patients, there have been no definitive longitudinal investigations comparing peripheral blood lymphocytes (PBL) with peritoneal lymphocytes (PL) from these patients. Therefore, the purpose of this study was to prospectively compare the phenotypes of PBL and PL of CAPD patients and to determine if phenotypic changes occurred from the initiation of CAPD therapy over the subsequent 12 months. Patients were categorized into younger (< 60 years) or older (> 60 years) to determine if age-related factors contributed to differences in lymphocyte phenotypes. Blood and overnight peritoneal dialysate effluents (PDE) were obtained from 18 patients at the initiation of CAPD therapy and for 11 successive months. Fourteen lymphocyte subsets were quantitated using monoclonal antibodies and flow cytometry analysis. CAPD patients had significantly higher percentages of peripheral activated T (CD3+/HLA-DR+) cells and natural killer (CD57+) cells at the beginning of CAPD than normal controls. There were significantly greater percentages of B cells, activated T cells, and suppressor T (CD8+/CD11b+) cells and significantly fewer helper T (CD4+) cells in the PDE as compared with the patients' peripheral lymphocytes. No significant changes were observed over time in the phenotypes of PBL and only one PL phenotype showed significant changes with fluctuating levels of CD4+/CD45RA+ cells with continued peritoneal dialysis. In general, these findings suggest that although both PBL and PL activation is occurring in clinically uninfected patients, the characteristics of lymphocytes are stable over time.


Electroporation: a method for transferring genes into the gametes of zebrafish (Brachydanio rerio), channel catfish (Ictalurus punctatus), and common carp (Cyprinus carpio). Recombinant plasmids containing the Rous sarcoma virus long-terminal repeat (RSVLTR) promoter linked to either rainbow trout (Oncorhyncus mykiss) growth hormone 1 (rtGH1) or growth hormone 2 (rtGH2) cDNA were linearized and introduced into the fertilized eggs of zebrafish (Brachydanio rerio), channel catfish (Ictalurus punctatus), and common carp (Cyprinus carpio) by both electroporation and microinjection. The latter two species had these rainbow trout constructs (RSVLTR-rtGH1cDNA or RSVLTR-rtGH2) electroporated into both gametes (i.e., sperm and unfertilized eggs) prior to fertilization, into eggs shortly after fertilization, and at the first cell division stage. Survival was determined just after hatching and again between 3 and 5 months after hatching. Polymerase chain reactions and Southern blot analyses were used to detect those individuals carrying the introduced foreign genes 3 to 5 months after hatching, respectively. Individuals analyzed by both methods yielded identical results in a double-blind study. The electroporation results were compared with groups that were microinjected. Although survival was similar, electroporation tended to produce a greater number of transgenic individuals than the microinjection procedure, and many more eggs could be treated per unit time by electroporation than microinjection. Survival was better for common carp when electroporation was performed shortly after fertilization, whereas channel catfish fared better at the first cell division stage. Electroporation prior to and shortly after fertilization, and at the first cell stage appeared to generate a large fraction of transgenic fish. We cautiously conclude that electroporation is an efficient method for introducing foreign DNA into fish gametes and embryos and may be an ideal method for treating large numbers of gametes in a modest period.


Vascular endothelium and lymphocyte adhesion molecules in minor salivary glands of patients with Sjogren's syndrome. The aim of this study was to examine the distribution and types of adhesion molecules expressed over endothelial cells and the ligands present on lymphocytes which infiltrate exocrine glands in patients with Sjogren's syndrome. Minor salivary gland biopsies were examined from twelve patients with Sjogren's syndrome and eight normal subjects for the presence of adhesion molecules using monoclonal antibodies and an Indirect Immunoperoxidase technique. There was an increased expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on endothelial cells, lymphocytes, fibroblasts and salivary gland epithelial cells. In addition we documented the expression of endothelial leukocyte adhesion molecule-1 (ELAM-1) on endothelial cells in salivary glands from patients but not the controls. Many of the endothelial cells expressing these adhesion molecules in patients with Sjogren's syndrome had the morphological appearance of high endothelial venules. V-CAM-1 was shown to be present in some of the salivary biopsies from patients with Sjogren's syndrome. Lymphocytes infiltrating salivary glands strongly express LFA-1 (CD11a/CD18) molecules. Some infiltrating lymphocytes, and most monocytes, expressed C3bi-R (CD11b/CD18) and the p150.95 (CD11c/CD18) antigens on their cell surface. The results of this study reveal the enhanced expression of vascular endothelial and lymphocyte adhesion molecules on the minor salivary glands of patients with Sjogren's syndrome. The presence of such receptors and their putative ligands indicate an important role for these molecules in the pathogenesis of Sjogren's syndrome.


Prevalence of anti-cytomegalovirus antibodies in a children population of Buenos Aires. The seroprevalence of anti-Cytomegalovirus antibodies in a selected children population was studied by an enzyme-immunoassay (ELISA) prepared in our laboratory. Sera from 207 children from middle socio-economic classes were studied. Children were divided into the following groups: Group 1: cord sera (n = 87); Group 2: children aged 13 months to 6 years (n = 54); Group 3: children aged 6-15 years (n = 66). Overall seroprevalence was 46.3%. The seropositivity and ELISA index titers for the three groups were, respectively: Group 1, 55%, mean = 2.16; Group 2, 90.7%, mean = 5.15; Group 3, 59%, mean = 2.49. Group 2 exhibited higher seropositivity (p < 0.0001) and higher index titers (p < 0.0001) than the other two groups. These results suggests that primoinfection with Cytomegalovirus in this population occurs in children aged 13 months to 6 years (Group 2). However, the high percentage (55%) of cord blood without anti-Cytomegalovirus antibodies suggests a risk for congenital infection or primary infection for those newborn who required blood transfusions or were fed with bank milk. Further studies are needed to determine the impact of Cytomegalovirus infections in populations from different socio-economic classes, in congenital infections, the prevalence of antibodies in blood banks and their frequency in immunocompromised patients.


The role of plasminogen activation in smooth muscle cell migration after arterial injury. The migration of smooth muscle cells from the media to the intima that occurs after balloon catheter injury to the rat common carotid artery has been quantified by an electron microscopic surveying technique. These vessels have also been assayed for plasminogen-activator activity, which was found to rise sharply 4 days after balloon injury. At this time point smooth muscle cells begin to migrate in appreciable numbers. In order to investigate whether there is a causal relationship between plasminogen-activator activity and smooth muscle cell migration, animals were dosed with tranexamic acid. This synthetic inhibitor of plasmin activity reduced smooth muscle cell migration by 73% (p < 0.05), indicating that plasmin activity is necessary for migration after balloon injury. Lisinopril, an inhibitor of angiotensin-converting enzyme, inhibited smooth muscle cell migration after balloon injury by 78% (p < 0.01) but did not influence plasminogen-activator activity. Taken together, these results show that plasmin is a necessary but not sufficient component in the pathway that leads to smooth muscle cell migration after balloon catheter injury in the rat.


Molecular basis of gonadotrophin action on human granulosa cell function. We studied in vitro the effects of Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH) on: 1) mature human granulosa cell proliferation and steroidogenesis; 2) intra-cellular second messenger (cAMP) generation, and the effects of cAMP analogues on cell function; and 3) mRNA expression of the rate limiting enzymes for progesterone and oestradiol synthesis namely: Cholesterol side chain cleavage (P450 SCC), Aromatase (P450 Arom); and 4) LH receptor mRNA expression. FSH maintained or stimulated, whereas LH markedly inhibited, basal granulosa cell proliferation. Steroidogenesis (oestradiol and progesterone production) was dose dependently increased by both gonadotrophins; with LH having the greater effect. However, only LH was able to induce maximal progesterone production. FSH generated about ten fold less cAMP than LH; and low and high doses of cAMP analogue were able to mimic FSH and LH effects respectively. Northern analyses showed that both FSH and LH were able to induce maximal P450 Arom mRNA expression, whereas only LH could stimulate maximal P450 SCC mRNA transcription. Maximal P450 Arom mRNA expression was associated with less cAMP generation than for P450 SCC. LH-R mRNA expression was induced by FSH but the strongest stimulatory effect was with LH. These results indicate that: 1) FSH and LH have markedly different effects on mature granulosa cell function; 2) the differential action of FSH and LH are dose dependently mediated through intracellular cAMP; 3) mRNA expression of P450 SCC and P450 Arom are differentially regulated by gonadotrophins and intracellular cAMP; and 4) LH was the most potent inducer of its own receptor mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)


Animal models in micromanipulation.

Animal models in micromanipulation. Micromanipulation is a useful technique for various studies of reproductive biology. Using this technique, we investigated the role of cAMP in the regulation of oocyte maturation. Anti cAMP serum was microinjected into oocyte cytoplasma. Immature oocytes resumed meiosis after microinjection and this result shows oocyte cAMP to be important for the intrafollicular meiotic arrest of oocyte and its decrease to cause resumption of meiosis. We also determined maturation promotion factor (MPF) activity in the mouse egg. Microinjection of cytoplasma from mature egg induced geminal vesicle break down of immature oocyte in the presence of dbcAMP. In addition, we detected MPF activity in cytoplasma of metaphase II oocyte. Some of the initial events of sperm-induced egg activation are accompanied by hydrolysis of phosphatidyl inositol which generates inositol trisphosphate (IP3). Mouse eggs microinjected with increasing concentration of IP3 revealed concentration dependent increase in conversion of the zona glycoprotein ZP2 to ZP2f. Modification of zona pellucida elicited by microinjection of IP3 are similar to those that occur following fertilisation. We also microinjected some cytoplasma of morula or 2 cell mouse embryo into 1 cell embryo of ICR mouse. After microinjection and culture, most of the embryo that reached 4 cells stage and 2 cell block of ICR mouse embryo was released significantly. These results suggest that some cytoplasmic factor(s) is a requisite for the development of embryo after fertilisation.


[Salmonella m'bandaka isolated in a nursery]. A epidemic of enteric pathogens bacteria occurred in december 1989 and caused two deaths in a nursery. There were many investigations between december 1989 and september 1990 trying to clarify this epidemic context. A new serovar of Salmonella had for the first time been isolated from babies' feces in Algeria. Salmonella m'bandaka has been identified in more than 50% of analysis. During an hygienic investigation in this nursery the above Salmonella m'bandaka was isolated in a open physiologic solution flask.


[Detection of human papillomavirus (H.P.V.) DNA in genital lesions using molecular hybridization]. Detection of human papilloma virus in genitals lesions by molecular hybridization. Some H.P.V. types are sexually transmitted and infect genital organs. We have used molecular hybridization to examine the distribution of H.P.V. 6 or II and H.P.V. 16 in benign, premalignant and malignant genital lesions from 344 patients. The frequency of H.P.V. 16 positive cases increases as the cervical lesions progress to malignancy: 57/78 are positive (73%) in the carcinomas, 29/83 are positive (35%) in mild or moderate dysplasia. The majority of benign condylomata acuminata harbors DNA of other types, namely H.P.V. 6 and II.


[Diagnosis of peripheral neuropathies: general characteristics of the population study]. The objective of the present investigation was to study the general characteristics of a population of 209 patients with peripheral neuropathies seen at the University Hospital of Ribeirão Preto from March 1985 to February 1987. Few studies have been devoted to the evaluation of patients in order to investigate the factors that may or may not contribute to the diagnosis of these conditions. The types of neuropathy detected were (in decreasing order of frequency): polyneuropathies, mononeuropathies and multineuropathies. Acquired forms were particularly outstanding in the first group and brachial plexus injuries in the second. Mean patient age was 36.4 years (range: 18 days to 81 years). Polyneuropathies prevailed among males and mononeuropathies among females, whereas multineuropathies equally affected males and females. Patient follow-up was less than 6 months for 52.6% of cases and less than one year for 7.3%. The significance and importance of these findings are discussed.


[Diagnosis of peripheral neuropathies: various factors of relevance for diagnosis]. The present study was undertaken to evaluate the influence of clinical examination and complementary tests on the diagnosis of peripheral neuropathies. Most of the patients (81.8%) were submitted to laboratory tests, 47.4% were submitted to electromyography, and 22.5% to biopsy. A syndromic diagnosis was made in 99.0% of the patients, topographic diagnosis in 98.6%, and etiological diagnosis in 73.2%. An average of 4.8 tests per patient were requested and 36 of the 93 different tests always gave normal results. The importance of the findings is discussed.


[Diagnosis of peripheral neuropathies: syndromic, topographic, and etiological diagnoses]. A retrospective study was conducted to identify the syndromic, topographic and etiological diagnoses made for a group of 209 patients with peripheral neuropathies. Anamnesis and clinical-neurological examination were of fundamental importance for the syndromic and topographic diagnoses. Electromyography played an important role, especially with respect to the topographic diagnoses. The etiological diagnoses depended on additional complementary tests such as: blood glucose levels and blood glucose tolerance test; nutritional evaluation; family evaluation; nerve, skin, pharynx and maxillary sinus biopsies; qualitative tests for the presence of porphyrins in urine; urinary levels of delta-aminolevulinic acid and porphobilinogen; and radiological examinations. The most frequently encountered polyneuropathies were those consequent to alcoholism or to diabetes, and those of the acute demyelinating inflammatory or hereditary type. Among the cases of mononeuropathy, the most frequently diagnosed conditions were carpal tunnel syndromes, traumatic injury to the VII cranial nerve, and trigeminal neuralgias. Leprosy, brachial plexus injury and thoracic outlet compression syndrome predominated among the multineuropathies.