[Septic erosion of the internal carotid artery and retrostylian phlegmon. Apropos of a case]. The vascular complications of peritonsillar phlegmons have become exceptional. On the basis of a recent case, the authors sum up the criteria of severity, including: white puncture sample, paralysis of the 9th, 10th, 11th, 12th cranial nerves and of the cervical sympathetic nerve. Computed tomography allows not only refining the topographic diagnosis, but even sometimes diagnosing a pseudoaneurysm before it is fissured. At this stage, intraoperative radiology may probably prevent the unavoidable secondary rupture. If it cannot be used, preventive ligation must be proposed. In the absence of cataclysmic hemorrhage, this easier procedure usually does not cause any irreversible neurological deficit. If performed in emergency, it may entail a major risk, not only a neurological risk, but a vital risk as well.


[Vocals in silence and noise. A simple test of resistance of intelligibility in noisy environment]. We have all noticed that there was no coincidence between the conventional audiometric tests--tonal, vocal, Metz tests--and the degree of impairment of understandability in noisy environments that the patients report. Some of them handle this problem better than these conventional tests suggest, others less well. The aim of this study is to take account of this dominating functional complaint: impairment in noisy conditions, and to assess it in order to follow up its evolution after medical, surgical and prosthetic treatments. The aim of the authors has been to describe an easy examination to be implemented in any ENT surgery fitted with a free-field vocal testing equipment. The results show that this test cas differentiate between "noise-resistant" subjects and those that do not "resist" well. The discussion defines the limitations of this test, which are due to its deliberate simplicity, and the caution required for its psychoacoustic and physiological interpretation. The conclusion confirms its merits, since it can discriminate and help choose more accurate tests--temporal tests, frequency selectiveness charts, twin-ear tests, cognitive AEP.


Determination of urinary glucose by a flow injection analysis amperometric biosensor and ion-exchange chromatography. A practical biosensor system has been developed for the determination of urinary glucose using a flow-injection analysis (FIA) amperometric detector and ion-exchange chromatography. Glucose oxidase was immobilized onto porous aminopropyl glass beads via glutaraldehyde activation to form an immobilized enzyme column. On the basis of its negative charge at pH 5.5, endogenous urate in urine samples was effectively retained by an upstream anion-exchange resin column. The biosensor system possessed a sensitivity of 160 +/- 2.4 RU microM-1 (RU or relative unit is defined as 2.86 microV at the detection output) for glucose with a minimum detection level of 10 microM. When applied for the determination of urinary glucose, the result obtained compared very well with that of the widely accepted hexokinase assay. The immobilized glucose oxidase could be reused for more than 1000 repeated analyses without losing its original activity. The reuse of the acetate anion-exchange column before replacement would be about 25-30 analyses. Acetaminophen and ascorbic acid were also effectively adsorbed by the acetate anion exchanger. The introduction of this type of anion exchanger thus greatly improved the selectivity of the FIA biosensor system and fostered its applicability for the determination of glucose in urine samples.


Glucose biosensor using glucose oxidase immobilized in polyaniline. A biosensor for glucose utilizing kinetics of glucose oxidase (EC 1.1.3.4.) was developed. The enzyme was immobilized on polyaniline by covalent bonding, using glutaraldehyde as a bifunctional agent. The system showed a linear response up to 2.2 mM of glucose with a response time of 2.5-4.0 min. In addition, the immobilized enzyme had a higher activity between pH 6.5 and 7.5. The system retained 50% of its activity after 30 d of daily use. The optical absorption spectra of the polyaniline/glucose oxidase electrode after glucose had been added to the buffer solution showed that the absorption band around 800 nm had changed considerably when glucose was allowed to react with the electrode. This optical variation makes polyaniline a very promising polymer for use as a support in optical sensor for clinical application.


Purification and characterization of a milk clotting protease from Mucor bacilliformis. An acid protease having milk clotting activity has been isolated from Mucor bacilliformis cultures. The enzyme was basically purified by ionic exchange chromatography. An average yield of 29 mg purified product was obtained from 100 mL crude extract. As purity criteria, SDS-PAGE, reverse-phase HPLC, and N-terminal analysis were performed. The protease is a protein composed of a single polypeptide chain with glycine at the N-terminus. The mol wt is approx 32,000, and its amino acid composition is very similar to those of other fungal proteases. As expected, its clotting activity was drastically inhibited by pepstatin A action. On the other hand, its instability against heat treatment and its clotting/proteolytic activity ratio indicate that it may be considered as a potential substitute for bovine chymosin.


Recurrent cutaneous erythralgia and arthralgia. Two cases are reported of Vietnamese men who presented in young adult life with recurrent, painful, erythematous patches (which we have termed "erythralgia") over and adjacent to joints and accompanied by marked constitutional symptoms of malaise and lethargy, arthralgia and in one patient, fever. In the other, from the onset of the disease there were nodules over the bony prominences and in the interphalangeal regions of the fingers. The duration of the disease was over 12 years, the duration of each episode without therapy was one week and the interval between episodes was one to two weeks. In addition the patients showed a raised ESR and peripheral neutrophil leucocytosis of over 70%. There was a rapid response, within hours, to non-steroidal anti-inflammatory agents. Skin biopsies taken at varying stages of the disease episode failed to demonstrate neutrophils thereby failing to satisfy one major criterion of Sweet's Syndrome. Direct immunofluorescence studies were negative. Biopsy of the nodules did not show rheumatoid pathology. The serum rheumatoid factor was negative. Investigations failed to demonstrate any recognised pattern of cutaneous or rheumatologic disease; infections such as borreliosis were excluded. Both patients showed evidence of past hepatitis B infection. As recurrent painful cutaneous erythema is an uncommon phenomenon in dermatology except where the patient is suffering from recurrent cellulitis of the lower limbs, the patients reported here exhibit a pattern of disease not previously described.


Ultrastructural modifications of patellar tendon fibres used as anterior cruciate ligament (ACL) replacement. Using transmission electron microscopy, patellar tendons that had been autografted to replace the ACL were studied. Follow-up biopsies, performed at 6, 12 and 24 months after reconstructive surgery demonstrated that the autograft patellar tendons had undergone considerable change. After 6 months, the large collagen fibrils were less numerous and more widely spaced. The spaces were occupied by dense colonies of very small, newly-formed collagen fibrils and were rich in glycosaminoglycans. Small elastic fibres, fibrocytes, round cells with abundant rough endoplasmic reticulum and macrophage-like cells were scattered among the collagen fibrils. At 12 months, sporadic clumps of large collagen fibrils were seen between the compact bundles of small, uniform collagen fibrils. Both elastic and oxytalan fibres were observed; round cells with abundant rough endoplasmic reticulum were the most prevalent cell type. At 24 months, the tissue had the appearance of a normal ligament. The small uniform collagen fibrils had formed large, compact bundles that were prevalently arrayed parallel to the long axis. Both elastic and oxytalan fibres were observed and the numerous cells present exhibited the same morphological features as those observed at 12 months after surgery. The appearance of compact collagen bundles, the abundant elastic system and the abundance of active cells observed in the patellar tendon autograft 24 months after implantation, suggest that this type of tissue is a valid functional ACL substitute of a knee required to perform normal mechanical activity.


A comparative study of gluconolactone versus benzoyl peroxide in the treatment of acne. Alpha hydroxy acids (AHA's) or "fruit acids" are a special group of organic acids found in many natural foods. They have been described in the literature for the treatment of a number of conditions in which abnormal keratinization consistently contributes to pathogenesis. These include the icthyoses, warts, psoriasis, eczema and acne. We have performed a double-blind clinical trial on 150 patients to evaluate the efficacy and skin tolerance of the alpha hydroxy acid gluconolactone 14% in solution (Nuvoderm lotion) in the treatment of mild to moderate acne when compared with its vehicle (placebo) and 5% benzoyl peroxide lotion. The results of this study showed that both gluconolactone and benzoyl peroxide had a significant effect in improving patients' acne by reducing the number of lesions (inflamed and non-inflamed). Furthermore, fewer side-effects were experienced by patients treated with gluconolactone when compared with benzoyl peroxide.


Ultrastructural observations on blood vessels surrounding normal and regenerating spinal cord in newt. The ultrastructural analysis of capillaries surrounding normal and regenerating caudal spinal cords of two species of newt (Triturus vulgaris and T. cristatus) is reported. Around normal spinal cords, capillaries were generally continuous. Surrounding the regenerating spinal cords the various capillaries of the regenerating blastema appeared discontinuous with small or broad gaps along the capillary wall. This was seen even after two months of tail regeneration when the spinal cord was similar to the normal and many axons were myelinating. These morphological findings suggest that during tail regeneration in newts the blood-brain barrier is not very effective. Also extravasating mature and immature blood cells were observed inside regenerating capillaries. Therefore growing capillaries can exchange metabolites and, possibly, growth factors with the nervous tissue and the other regenerating tissues.


Morphologic study of the gastric mucosa during Helicobacter pylori infections. The purpose of the present, study was to underline the importance of the use of SEM in the evaluation of Helicobacter pylori (HP) - Induced gastritis. Gastric biopsies from eleven patients affected by HP infections were examined using Light Microscope (LM), Transmission Electron Microscope (TEM) and Scanning Electron Microscope (SEM). SEM allowed for the localization of even small groups of bacteria and to demonstrate the many morphologic changes due to the infective phlogosis. The signs of cellular suffering and the relationship between bacteria and microvilli are of particular interest.


Congenital inclusion dermoid cysts of the scalp. The natural history of congenital inclusion dermoid cysts of the scalp is unknown. We report three cases of this condition, which has been followed from birth for up to ten years. Dermoids are congenital subcutaneous cysts, which gradually flatten and scar over a number of years. The lesions are covered with skin showing focal alopecia but they may be surrounded by a collar of hypertropic hair. Later in life flattened cysts may be mistaken for aplasia cutis, but the history of a cyst at birth allows the clinician to distinguish these two conditions. As these cysts have a potential for intracranial extension, this is an important clinical entity.


Pancreatic arteries and anatomicosurgical segments in dogs. The distribution of the arteries supplying the pancreas was studied in 22 adult dogs (7 females and 15 males) of mixed breed. The pancreas was divided into 2 lobes, 4 sectors and 6 anatomicosurgical segments. These segments are defined as territories recognizable anatomically and surgically removable. The division and subdivision of the pancreas and the segmental arteries were the following: Left Lobe: Omental sector: I. Proximal segment: splenic a. II. Middle segment: splenic a. III. Distal segment: gastroduodenal and right gastro-omental Interpapillary sector: IV. Juxtaduodenal segment: cranial pancreaticoduodenal a. Right Lobe: Distal sector: V. Distal segment: cranial pancreaticoduodenal a. Proximal sector: VI. Proximal segment: caudal pancreaticoduodenal a.


Subcutaneous fat necrosis of the newborn complicated by hypercalcaemia and thrombocytopenia. Subcutaneous fat necrosis of the newborn is an uncommon but distinctive condition which appears in the first six weeks of life, associated with variable degrees of hypercalcaemia and which resolves spontaneously over months. We report a case of subcutaneous fat necrosis of the newborn following perinatal distress and complicated by thrombocytopenia and hypercalcaemia.


Tea tree oil in the treatment of tinea pedis. Tea tree oil (an essential oil derived primarily from the Australian native Melaleuca alternifolia) has been used as a topical antiseptic agent since the early part of this century for a wide variety of skin infections; however, to date, the evidence for its efficacy in fungal infections is still largely anecdotal. One hundred and four patients completed a randomized, double-blind trial to evaluate the efficacy of 10% w/w tea tree oil cream compared with 1% tolnaftate and placebo creams in the treatment of tinea pedis. Significantly more tolnaftate-treated patients (85%) than tea tree oil (30%) and placebo-treated patients (21%) showed conversion to negative culture at the end of therapy (p < 0.001); there was no statistically significant difference between tea tree oil and placebo groups. All three groups demonstrated improvement in clinical condition based on the four clinical parameters of scaling, inflammation, itching and burning. The tea tree oil group (24/37) and the tolnaftate group (19/33) showed significant improvement in clinical condition when compared to the placebo group (14/34; p = 0.022 and p = 0.018 respectively). Tea tree oil cream (10% w/w) appears to reduce the symptomatology of tinea pedis as effectively as tolnaftate 1% but is no more effective than placebo in achieving a mycological cure. This may be the basis for the popular use of tea tree oil in the treatment of tinea pedis.


Linear scleroderma with severe leg deformity. Linear scleroderma is an unusual form of localised scleroderma, mainly affecting the legs and occurring primarily in children. Sometimes the linear lesions may extend to involve the underlying muscles and bones, with severe disturbances in growth and possibly flexion deformities of the legs. In this study, two cases suffering from linear scleroderma of the legs are presented.


Dermatophyte and non-dermatophyte onychomycosis in Singapore. Onychomycosis is caused by dermatophytes, moulds and yeasts. It is important to identify the non-dermatophyte moulds as they are resistant to the usual anti-fungals. A prospective study was undertaken in the National Skin Centre, Singapore to study the pattern of dermatophyte and non-dermatophyte onychomycosis. 53 male and 47 female patients seen between June 1990 and June 1991 were entered into the study. Direct microscopy was done and the nail clippings were cultured. Toe and finger nails were equally infected. Dermatophytes were isolated from 21 patients namely, T. rubrum (12/21), T. interdigitale (5/21), T. mentagrophytes (3/21) and T. violaceum (1/21). Candida onychomycosis occurred in 39 patients and was caused by C. albicans (38/39) and C. parapsilosis (1/39). 37/39 patients had associated paronychia. 5 types of moulds were isolated from 12 patients, namely Fusarium species (6/12), Aspergillus species (3/12), S. brevicaulis (1/12), Aureobasilium species (1/12) and Penicillium species (1/12). Although the clinical pattern and microscopy may predict the type of organisms, in practice this is difficult. Only cultures were confirmatory. 28% (28/100) had negative cultures despite a positive microscopy, and moulds (12/100) grown might be contaminants rather than pathogens.


Scytalidium hyalinum isolated from the toe nail of an Australian patient. The isolation of Scytalidium hyalinum from the toe nail of a patient from Melbourne is reported. This is the first record of the isolation of this fungus from a clinical site in Australia. A brief history is given of the occurrence of Scytalidium hyalinum and the related fungus, Hendersonula toruloidea, in tinea pedis and tinea unguium in immigrants to the United Kingdom from tropical countries. Attention is drawn to the possible presence of these dermatophyte-like infections in patients in Australia.


Four non-endemic New Zealand cases of chromoblastomycosis. The majority of cases of chromoblastomycosis are reported from tropical to subtropical countries; only one previous case being reported from New Zealand. Four non-endemic cases in Pacific Island patients are described. All of the New Zealand cases were caused by Fonsecaea pedrosoi. In the present report, one patient was successfully treated by excision of the lesion followed by skin grafting. Another was treated with 200 mg ketoconazole daily for 10 weeks with no obvious improvement. No follow-up on the treatment of this case nor of the remaining two patients is available. This disease must be included in the differential diagnosis in patients who present with chronic lesions affecting the skin and subcutaneous tissues.


Incidence of Aeromonas isolated from diarrhoeal children and study of some virulence factors in the isolates. Stool samples from 305 children with diarrhoea and equal number of age and sex matched non-diarrhoeal control children, less than 5 years of age, were examined during the period from Sept 1988 to April 1989. Aeromonas spp. were isolated from 37 (12.1%) diarrhoeal and 05 (1.6%) control cases. Out of 37 diarrhoeal isolates 13 (35.1%) were A. hydrophila, 19 (51.1%) A. sobria and 05 (13.5%) A. caviae. All the isolated strains were tested for haem agglutination property and haemolysin production. Seventeen diarrhoeal and 05 control isolates were tested for cytotoxin production in He La cell line and enterotoxin production in rat ileal loop model and suckling mouse model. Chinese hamster ovary cell (CHO) assay and Gm-1 ELISA methods were also employed. Cytotoxin production was found in 82.5% of diarrhoeal and 40% of control isolates. Haemagglutination was found in 62.1% of Aeromonas isolated from diarrhoeal children and 20% from control children. Enterotoxin production was detected in 58.8% diarrhoeal and none of the control isolates by either of the methods. Of the virulence factors enterotoxin production was found to correlate well with enteropathogenicity but haemolysin, cytotoxin and haemagglutinin did not.


Role of radioiodine in management of thyroid cancer: experience with 70 cases. Results of 70 cases of differentiated thyroid carcinoma managed with I131 and surgery have been reported. These results add to the body of knowledge that already exists in the field of treatment of thyroid cancer with radioactive iodine. These results also indicate that the success of radioiodine therapy depends on adequate surgical removal of the thyroid tissue.


Utilization of health care facilities in Bangladesh. This study was conducted among 310 families at some urban and rural areas of Mymensingh district to know the pattern of utilization of available health care facilities by them. Out of 310 families, 150 were from 4 villages of Muktagacha thana (rural) and 160 were from Mymensingh pouroshava (urban). It was observed that 93.3 percent from rural and 95.6 percent of urban population were utilizing modern health care facilities. Of them 40.6 percent from urban and 33.3 per cent of rural areas were found to prefer private sector facilities. More than three-fourth of the urban children and half of the rural children of the families under study were found immunized. About 70 per cent of the town dwellers were availing MCH care. On the contrary the rate of utilization of MCH services by the village people was only 37.3 per cent.


Indirect fluorescent antibody test in the serodiagnosis of visceral leishmaniasis in Bangladesh. Indirect fluorescent antibody test (IFAT) was found to be 100% sensitive and 100% specific when tested with sera from 125 parasitologically proven kala-azar patients, 100 healthy controls and 50 sick control cases. Promastigotes of both L. enriettii and L. donovani as well as amastigotes of L. enriettii were found equally satisfactory as antigen for IFAT. From the results of the present study, it is concluded that IFAT is a highly sensitive as well as specific serological test for the diagnosis of kala-azar.


A psycho-social study on genito-urinary fistula. This study was done on a series of 132 vesico-vaginal fistula (V.V.F.) cases to assess the social factors that are related to this morbidity and its psycho-social effects on them. About 54% of the respondents developed VVF as an outcome of their first pregnancy and none of them had a living child. Of this 39% were in the age group of 15-20 years. About 68% were illiterate and 22% had received formal education for up to 5 years. Fifty two per cent of the subjects had a family income of up to Tk. 1,000 only per month. Almost all were Muslims (94.7%). Of the respondents 64.6% had home delivery by TBA and 72% had history of prolonged labour. Fifty six per cent of the subjects did not like to avail the health facilities of the nearby clinic/hospital. Lack of privacy, objection from husband/family and conduction of delivery by male doctor were mentioned as causes for not availing the facilities by this large group. Indifferent attitude of husband and in-laws, expressed willingness of husband for taking another wife, disturbed socio-psycho-sexual life and deterioration of general health were the after effects of the morbidity at individual, conjugal and community level of the respondents.


Rhesus genotype frequency in Bangladeshi population. The prevalence of Rhesus genotypes in Bangladesh has been studied and several important findings were observed. This being the initial report, includes a population of 1600 only. By using five Rh antisera (Anti-C, Anti-D, Anti-E, Anti-c and Anti-e) a genotype can be deduced since anti-d is not available. More often only a probable genotype can be suggested after reference to the known chromosome frequencies in the population. By using family studies in conjunction, it may be possible to determine genotype with certainty. The prominent Rhesus genotype was CDe/cDE (R1R2), i.e., 39.75%, Rhesus genotype cde/cde (rr) was found to be only 1.75%. The genotype cdE/cde (r"r) was not detected in the present series of Bangladeshi population. These results have been compared with the English and the Indian Bengalee Hindu Population.


Reproducibility and validity of laser flare/cell meter measurements as an objective method of assessing intraocular inflammation. Preoperative and postoperative anterior chamber reactions in a series of patients who had undergone cataract surgery were measured with a laser flare/cell meter (Kowa FC-1000, Kowa Instrument Corp, Japan) by two different technicians (A.M. and T.M.M.), and clinical assessments of inflammation were recorded. The average cell and flare readings of the two technicians were nearly identical at every time point, showing the laser flare/cell measurements to be highly reproducible. The correlations between laser flare/cell measurements and clinical assessments at postoperative time points were all highly positive (P less than .01), demonstrating the validity of the laser flare/cell measurements.


The T cell receptor gene and its association with human diseases. The genetic organization and protein structure of the T cell receptor (TCR)/CD3 complex are currently under investigation, and recent work has provided information about its assembly, expression and function. This article reviews what is currently known about the structure and assembly of the TCR/CD3 complex. The TCR chains are members of the immunoglobulin gene superfamily and are generated by combinatorial associations of V, J, D, and C genes. The presence of certain gene rearrangements within these chains has been associated with lymphoproliferative disorders, autoimmune disease and immunodeficiencies. TCR rearrangements can be useful in the diagnosis of lymphoproliferative disorders and in the identification of patients who will subsequently relapse, once in remission. With respect to autoimmune disease, the possibility now exists of immunotherapy with TCR designer polypeptides to prevent disease. In patients with primary immunodeficiencies secondary to defects in expression of the TCR, the possibility of somatic gene therapy now exists. As more information unfolds about the role that TCR gene rearrangements have in various diseases, new insights are gained into better diagnosis and treatment.


Altered expression of blood group A and H antigens on red cells from an acute leukemic patient. Alternate expressions of the blood group A and H antigens on red cells are described in a patient with acute myelocytic leukemia. The patient's red cells showed mixed field agglutination with anti-A and anti-H sera and lectins, and no agglutination with anti-B serum. The agglutinability of the A red cells with Dolichos biflorus lectin was between A1 and A2 (A intermediate). Inagglutinable red cells were separated with anti-A agglutinin, and the proportion was about 80% of total cells. The agglutinating activity with Ulex europaeus anti-H of red cells, which were inagglutinable with anti-A, was 16 times weaker than that of group O cells. The weaker reaction with Ricinus communis lectin and the stronger reaction with Psathyrella velutina lectin on the inagglutinable cells with anti-A than those on the group O cells suggest that fucosyl alpha (1-2) and galactosyl beta (1-4) residues at the nonreducing end of carbohydrate chains of H antigens on the red cells were diminished, and N-acetylglucosaminyl beta (1-3) residues were sequentially exposed. His saliva contained A and H substances in normal amounts of a secretor. Serum alpha-N-acetylgalactosaminyltransferase activity which converts O red cells to A red cells was the same as those in sera from A1 individuals. These results suggest that the synthesis of H precursors is partially blocked in this patient's red cells.


Genetic polymorphism of IgG in the mink. IX. High proportion of allotype-producing lymphocytes in individuals with minor level of allotypes H3 and H4 in serum. The levels of mink C gamma-allotypes (H3, H4, H6 and H8) were determined in sera, and the proportion of the corresponding allotype-synthesizing B cells was estimated in peripheral blood, spleen and mesenteric lymph nodes. Individual differences in H6 levels and, possibly, those in H8 were entirely dependent on the proliferation degree of the corresponding clone of B cells and also determined by the dosage of the structural gene. There was no correspondence between the great numbers of H3+, H4+ cells and low levels of H3 and H4 allotypes in the sera of the majority of minks with their minor expression. A possible cause of this discrepancy may be a blockade of the secretion of IgG by H3+, H4+ cells. There exists most likely a gene (or genes) controlling the blockade of IgG secretion. The regulation of C gamma-allotype expression is presumably effected in a manner specific to each of the allotypes.


HLA-A region in highly sensitized patients: another immune response gene region. HLA haplotypes were assigned by family typing in 94 prospective kidney transplant recipients. An HLA-A region of the HLA-A, B, DR haplotypes was found in association with high levels of antibodies against lymphocytes. There was a significant difference in the frequency of HLA-B8-positive haplotypes among the patients with regard to the distribution of HLA-A alleles (p = 0.0028); on the same haplotype the A1 and B8 alleles were found in moderately and weakly sensitized patients and HLA-A alleles other than A1 were present with B8 in highly sensitized patients. A significantly higher number of highly sensitized patients when compared with moderately sensitized patients had haplotypes with HLA-A alleles in negative linkage disequilibrium with HLA-B alleles (77 vs. 10%, p = 0.014). The results are in good agreement with a previous suggestion that the interaction between the HLA-A class I and class II regions regulates the immune response. Determination of HLA haplotypes might identify patients at high risk for broad and persisting sensitization.


Group-specific component is not only a vitamin-D-binding protein. The vitamin-D-binding protein (DBP), also called group-specific component, is well known for two main reasons: its genetic polymorphism, and its binding affinities for actin and vitamin D compounds. In recent years, additional binding affinities have been described for this puzzling molecule, without any significant biological explanations being given for these observations. The molecular genetic data for DBP are analyzed in order to show that the affinities for vitamin D are supported by the genetic variability. The molecular evolution of the protein shows that the ancestral gene was present long before the development of related genes, such as those for albumin and alpha-fetoprotein. Other affinities for actin, C5a-desArg and for a B lymphocyte mitogen are also discussed. DBP is mainly present in the circulating blood as an apoprotein. The cytoplasmic presence of DBP has not been confirmed, and the major question today is to understand the biological role of this protein. In the last part of the review, the discussion focuses on relating the different binding affinities of DBP to its biological activities. Avenues for future research are also outlined: these include DBP metabolism, the differentiation of macrophages, and the activity of DBP during embryonic development.


[The stimulation of the delayed hypersensitivity reaction by the venom of the blunt-nosed viper Vipera lebetina and by its liposomal form]. Native poison of middleasia viper Vipera lebetina has been included into liposomes in order to get an effective preparation for immunotherapy. The preparation reduces the risk of complications taking place during the use of traditional methods. The immunomodulating action of the liposomal form of viper poison has been investigated on the model of reaction of hypersensitivity of delayed type. Together with the stimulation of functional activity T-cells, the absence of suppressive and toxic actions while using the liposomal preparation of poison has been discovered. It is suggested that the observed stimulating effect in connection with immune reactions is due to synergism of action of components of poison liposomal form and activation of T-cells and macrophage, taking part in immune response to the antigenic stimulus.


Macrophages capable of inducing anterior chamber associated immune deviation demonstrate spleen-seeking migratory properties. Antigens injected into the anterior chamber of the eye generate a deviant immune response (Anterior Chamber Associated Immune Deviation--ACAID) characterized by impaired delayed hypersensitivity and lack of complement-fixing antibodies. Both the antigen-containing eye and an intact spleen are required for ACAID induction. The eye's contribution takes the form of an antigen-specific, ACAID-inducing signal associated with blood-borne F4/80+ macrophages. Macrophages capable of carrying an ACAID-inducing signal can be harvested directly from the iris and ciliary body, or can be created by exposing F4/80+ peritoneal exudate cells to aqueous humor or to supernatants of cultured iris and ciliary body cells. In the present study, F4/80-bearing macrophages from the peritoneal cavity were exposed in vitro to supernatants of cultured iris and ciliary body cells and then labelled with PKH-2 prior to intravenous infusion into naive, syngeneic recipients. The pattern of distribution of these cells in spleen, lymph nodes, and blood was compared with similarly labeled cells exposed in vitro to medium alone. The results reveal that, compared to conventional peritoneal exudate cells, macrophages that are endowed with ACAID-inducing properties (by exposure to supernatants of iris and ciliary body cell cultures) preferentially migrate to the spleen following their intravenous inoculation into syngeneic recipients. Moreover, when injected intravenously into asplenic mice, macrophages with ACAID-inducing potential accumulate excessively (compared to their conventional counterparts) in the peripheral blood.(ABSTRACT TRUNCATED AT 250 WORDS)


[The effect of hypoxia and of subsequent baro-oxygenation on the function of the microsomal oxidation system in the rat liver]. The increase of cytochrome P-450 by 34% and its catalytic activity with substrate amidopyrine by 57% as compared with control has been shown under hypoxia (0.029 MPa, 1 h). Hyperoxia (0.2 MPa, 1 h) increases the metabolism of amidopyrine by 148%, benzo[a]pyrene by 158% and aniline by 114% and consecutive affection of hypoxia and hyperoxia--by 247, 45 and 138% correspondingly at fixed cytochrome P-450 amount in both series. The amount of diene conjugates and Schiff's bases under hypoxia increases by 40 and 69% correspondingly, the activity of SOD and catalase decreases by 25 and 23%. The activity of hyperoxia raises the diene conjugate content by 19% at all this SOD activity increases by 95%. Consecutive affection of hypoxia and hyperoxia increases the level of diene conjugates and Schiff's bases by 26 and 23% correspondingly, without changing SOD and catalase activity. The relative microsomal viscosity of lipid layer and zones of enzyme-lipid contacts decreased by 20 and 24% under hypoxia, but under hyperoxia and consecutive affection and hypoxia and hyperoxia it increases by 29-28% and 56-40% correspondingly.


Differential effect of aging on membrane immunoglobulin (mIg)-mediated endocytosis in the inductive and effector sites of the mucosal immune system. The effect of aging on the endocytosis of anti-immunoglobulin (Ig) antibody as ligand by membrane Ig receptors (mIg) of B cells in the spleen, the mesenteric lymph nodes (MLN), and the Peyer's patches (PP) was investigated. Horse radish peroxidase (HRP) labelled (Fab')2 anti-mouse Ig specific for IgM, IgG, and IgA was used as the ligand. The rate of mIg mediated ligand endocytosis by aged B cells was significantly reduced in the PP as compared to the young group. In contrast, there were no age-related differences in the rate of mIg-mediated ligand endocytosis by B cells in the spleen and MLN. After 2 hr of incubation, about 70-80% of ligand added was internalized by splenic and MLN B cells from both young and old mice. Aged PP B cells showed significantly slower rate of ligand internalization as compared to those cells from young mice. This effect was pronounced at 30 and 60 min after incubation. Young PP B cells were found to internalize about 50% of the ligand within 30 min, while it took 60 min for aged B cells to internalize the same amount. The age-related rate of mIg-mediated endocytosis by B cells in the MLN, as opposed to a slower rate of endocytosis by B cells in the PP, emphasizes its distinct nature as a mucosal site.(ABSTRACT TRUNCATED AT 250 WORDS)


Changes in the configuration and the dimensions of the fossa hypophysealis in the rat (Rattus rattus norvegicus) dependent on the age, weight and individual size of the skull. The aim of our work was to describe the fossa hypophysealis in the most common laboratory animal--in the rat, to measure its dimensions, to determine its stereotactic coordinates and to find the dependence of these coordinates on the age, weight and individual size of the skull in different rats. From this measurement we obtained data on the growth and possible shifts of the fossa hypophysealis but also found data facilitating the selection of animals to stereotactic operations so that the hit of the hypophysis be the most probable. There are suitable coordinates for bilaterally stereotactic intervention into the middle female rats hypophysis in conclusions of our work.


Adjuvant effects of freely ingested cholera toxin on systemic antibody and DTH responses to protein antigen. Recent evidence suggests that immunological handling of antigen in the gut may be different when animals voluntarily ingest antigen in their drinking fluid. Therefore, we investigated whether the adjuvant effects of CT were evident in mice that voluntarily ingested CT together with keyhole limpet hemocyanin (KLH) in 1.0 ml chocolate milk. Initially, it was found that ingestion of 2 mg KLH for up to four times (one ingestion per week) did not induce serum IgG anti-KLH antibody; however, KLH-specific IgG was detected if KLH was ingested together with 10 micrograms CT. Furthermore, 50 days after only one ingestion of CT+KLH, the serum IgG response to intraperitoneal challenge with 100 micrograms KLH was significantly elevated with respect to the response of mice who previously had ingested either KLH alone, CT alone, or drinking fluid only. This observation was repeated in further experiments showing an enhanced IgG response to 100 micrograms KLH ip given 7 or 14 days after a single ingestion of 2 or 5 mg KLH mixed with different doses (0.5-20 micrograms) CT. The lowest effective CT dose for serum IgG anti-KLH adjuvanticity was found to be 1 microgram; the highest effective dose was 10 micrograms, there being no additive effect with 20 micrograms CT. It was also found that simultaneous ingestion of KLH (2 or 5 mg) with CT (0.5-20 micrograms) followed 7 or 14 days later by 100 micrograms KLH ip, increased the 24 hr footpad DTH response to 50 micrograms KLH administered 43 days after the ip challenge.(ABSTRACT TRUNCATED AT 250 WORDS)


An electron microscopic study of the development of the thymus anlage of athymic (nu/nu) mice. Using electron microscopy, we examined the anlage of dysgenetic embryo thymuses of nu/nu mice aged 14.5-15 days, 16 days and 18 days p.c., with thymus anlage of nu/+ mice serving as controls. On comparing both types, we noted differences at all intervals which increased in a time-related manner. Lymphoid cells were found only very occasionally in dysgenetic thymus anlage up to day 16 p.c. while there were no capillaries at all in any of the stages investigated. In epithelial reticular cells, undemarcated (membrane non limited) spaces of varying size and containing PAS+ material were found in the cytoplasm (glycogen-like particles seen in electron microscopy). Based on our findings, and on general assumptions, we believe that the primary process occurring in the dysgenetic thymus is abnormal epithelial stroma differentiation resulting not only in a lack of lymphoid cells but, also, in a limited or probably absent vascular bed.


Ultrastructural changes of neurons in dependence on the death cause in human brain. Autolytic changes in animal neurons 3 hours postmortem were compared with the changes in human material taken from the patients with ischemic heart disease. Relatively homogenous neuroplasm in the animal material was observed and the nuclei and nucleoli were present as well. Light artificial spaces were visible around the neurons. Marked vacuolization was in all cases of the human material. In some cases the nucleus with the nucleolus and mitochondria were still preserved. Majority of the neurons did not reveal the nucleolus and chromatin in their nuclei; destruction of the organelles and homogenization of the neuroplasm were dominant. We assume that the specific changes in the brain caused by the ischemic heart disease are different in comparison with the autolytic postmortal changes.


Nigrostriatal projections in the rat as demonstrated by retrograde transport of horseradish peroxidase. II. Projection to the caudal striatum. The distribution of nigral neurons projecting to the caudal and basal parts of the striatum was studied in 9 rats by means of the horseradish peroxidase labelling technique. Labelled neurons localized in the substantia nigra pars compacta were demonstrated throughout the antero-posterior extent of the nucleus. Most of them were found in the lateral half of the SNc. Labelled neurons localized in the substantia nigra part reticulata predominated in the caudolateral part of the SNr. Characteristic features included major perikaryal polymorphism and size range of the nigrostriatal neurons.


Regional accumulation of Pgp-1+ memory cells in senescent mucosal immune system. The proportion of memory cells expressing the Pgp-1 surface marker, and subsets of T cells expressing L3T4 (CD4+ helper cells), Lyt-2 (CD8+ suppressor/cytotoxic cells), LFA-1 (lymphocyte function-associated antigen-1), and interleukin-2 receptors (IL-2R) on the cell surface in the spleen, regional lymph nodes (PLN), mesenteric LN (MLN), bronchial or mediastinal LN (BLN), Peyer's patches (PP), thymus, and bone marrow (BM) was studied in C57BL/6J mice of varying ages. Monoclonal antibodies (Mabs) IM7.8.1, FD4, GK1.5, 3.155, and FD441.8 were used to measure Pgp-1, IL-2R, L3T4 Lyt-2, and LFA-1 expressions, respectively. Optimal dose and kinetic studies were determined. The percentages of positive cells were determined by monoclonal antibody staining and flow cytometry or immunofluorescence microscopy. Using flow cytometric analysis, we found significant age-associated increases in the percentages of Pgp-1+ cells in the MLN as compared with a slight, but not significant, increase in the spleen. There were significant age-related increases in the percentages of Lyt-2+ cells in the spleen with no change in the MLN. The percentages of cells with the other phenotypic markers, L3T4, LFA-1, and IL-2R did not change with age in the spleen or MLN. Using immunofluorescence microscopy, the percentages of Thy-1.2+, Lyt-1+, and Lyt-2+ cells in different anatomical immune tissues did not change with age, except in the BLN and PP where there were significant age-related declines of the percentages of Thy-1.2+ and Lyt-2+ cells in the BLN, and of Lyt-1+ cells in the PP. These results indicate elevated levels of Pgp-1+ memory senescent cells in the MLN and these age-related shifts or changes in T lymphocyte subsets with age could contribute to the conserved immune responsiveness of senescent mucosal T lymphocytes.


Ultrastructural aspects of synaptic adaptability in human brain. The ultrastructure of synapses in human brain which died with ischemic heart disease in various time after ischemic injury showed that the whole range of symptoms of compensatory character appears together with degenerative changes. The most important changes of presynaptic membrane consist of pinocytous invagination. Tubular structures in region of synaptic contact as well as on the surface of small invaginal axonal branches, dendrites and small spines are also found. We assume that plastic rebuilding of synapses have compensatory significance.


The ependyma of the goat. III. Organum vasculosum hypothalami. The presence of organum vasculosum hypothalami in the 3rd cerebral ventricle in goat has been confirmed. The surface of this organ is undulated, covered with cylindrical or cuboidal ependyma. Its rostral pole has simple, finger-shaped protrusions, the number of which increases during the "inactive" period (females: anestrus, males: out of season; both sexes: April), sporadically they occur in the mating season (females and males: October, November). Except for cilia and microvilli, no other supraependymal structures have been found. The organum vasculosum hypothalami of goats does not have dense capillary network and neither has "nucleus organi vasculosi hypothalami" been found.


The state of the microcirculatory bed after total ischaemia of the brain. An experimental ultrastructural study. The study was focused on the changes in morphological structure of cerebral microcirculation after two stages of 7 min dog's total brain ischaemia followed by 24 recirculation. In the first experimental group (brain blood pressure 2.5-3.0 kPa), there was observed ultrastructural picture of damaged microvessels, including dilated and irregularly shaped lumens, thick finger-like endothelial processes, dark osmiophilic cytoplasm of the endothelial cells with light spaces, clusters of ribosomal structures, impairment of endoplasmic reticulum and mitochondria, dilated tight junctions, irregular and thickened basement membranes. The alteration of astrocytes consisted of accumulation of beta-glycogen particles and lipofuscin and altered lysosomal structures. On the other hand, in the second experimental group (brain blood pressure 1.0-1.5 kPa) the signs of impaired microcirculation were found. Type A pattern of vessel damage was delineated by dilated capillary lumen, despite the presence of marked perivascular oedema. Type B represented the no-reflow phenomenon. Type C was defined by a conspicuous lobular nucleus of endothelial cells obstructing the lumen of the capillary. Type D was characterized by ischemically damaged erythrocytes, despite the adequate perfusion fixation. Finally, type E included necrotic endothelial cells and endothelial blebs.


A freeze-fracture study on the effect of neopybuthrin on the intestinal epithelial cells of Tilapia nilotica. Freeze-fracture replicas of the plasma membrane and tight junctions (Tj) of intestinal epithelial cells were studied in Tilapia nilotica fish exposed to the pyrethroid insecticide, neopybuthrin. Exposing fishes to different repeated concentrations of 1/2 LC50 of neopybuthrin caused a significant decrease in the population density of IMPs in P- and E-faces. Tight junctions were also affected by neopybuthrin treatment. They appeared fragmented and discontinued, and their strands were fewer in number as compared with controls. Since the structure and number of Tj are major determinants of epithelial permeability, it is postulated that neopybuthrin treatment may affect the intestinal permeability of T. nilotica.


Study of the incidence of radicular grooves in maxillary incisors. The purpose of this investigation was to determine the incidence of radicular grooves in the upper incisors of 642 patients from the region of Ribeirão Preto, SP, Brazil. Radicular grooves, present in 3.9% of the patients, were found mainly on the lingual surface of the maxillary lateral incisor (3.0%). The maxillary central incisors showed radicular grooves on both the buccal and lingual surfaces with an incidence of 0.9%. It was not possible to relate the incidence of these grooves with race (white and negro) or with sex.


The effect of 1% chlorhexidine gel delivered with toothpicks on proximal dental plaque. A pilot study. The aim of this study was to determine the effect of 1% chlorhexidine gel delivered with toothpicks on interproximal dental plaque. Seven follow-up patients participated in two treatment periods of 1 week each, separated by a normal oral hygiene period of one week. The study had double-blind design. The plaque index by Silness and Löe (Acta Odontol Scand 22: 121-135, 1964) was scored on mesial, distal, buccal and lingual surfaces of each tooth after plaque disclosure, with an aqueous solution of erythrosine and the measurements were performed by the same examiner, at the initial visit and at the end of every experimental week. The ability to use toothpicks was checked and upgraded to the individual need. The participants were instructed to carry out their normal oral hygiene procedures, with placebo gel or 1% chlorhexidine gel delivered interproximally with toothpicks once daily. No significant differences in the measurement of plaque were noted between placebo gel and 1% chlorhexidine gel at interproximal areas. After treatment with 1% chlorhexidine gel, the mean distribution of plaque score 0 was increased significantly (P < 0.05), from 30.7 sites (52%) to 42 sites (71.1%) when all sites are taken into account and compared to the placebo period. 1% Chlorhexidine gel delivered by toothpick on interproximal areas had a limited effect on reduction of dental plaque.


Actinobacillus actinomycetemcomitans in Brazilian insulin-dependent individuals with diabetes mellitus. The prevalence of Actinobacillus actinomycetemcomitans (Aa) in subgingival plaque specimens from 26 insulin-dependent diabetes mellitus patients, 11-25 years of age, was determined between January 1987 and December 1989. One hundred and thirty subgingival plaque samples were collected with sterile periodontal curettes. The specimens were weighted, diluted, inoculated on trypticase-soy-serum-bacitracin-vancomycin agar medium (TSBV) and incubated under microacrophilic conditions. Aa was isolated from 2.3% of healthy periodontal areas in these patients, while the microorganism was found in 12.5% of the sites with gingivitis and in 2.6% of the periodontal pockets examined. Although biochemical tests used for the characterization of Aa strains showed homogeneous results, different biotypes were isolated from one or more periodontal sites in the same patient.


The influence of gross caries removal and temporary filling of dental caries with a zinc oxide eugenol cement on the level of mutans streptococci in saliva. The influence of gross caries removal and temporary filling of dental caries with a zinc oxide eugenol cement on the salivary level of mutans streptococci (MS) was studied in 14 children, 6 to 8 years of age. Forty-eight hours after filling all cavities, there was a significant decrease in the level of these cariogenic microorganisms. However, after 30 days, the salivary level of mutans streptococci was similar to that detected initially.


Free autogenous cartilage grafts to the mandible of rats-histological study. The present study was designed to histologically evaluate the behavior of free autogenous cartilage grafts to the mandible of rats. A 3-mm segment was removed from the last rib of male adult rats and transplanted fresh to a receptor bed prepared on the mandibular ramus. The results showed that the grafts maintained their vitality up to 120 days and the perichondrium was biologically integrated to the osseous bed. Appositional growth of the grafts was found. New bone formation was observed in close proximity to the grafts, but newly formed trabeculae did not arise from perichondrium.


Method of preparing inter-mouth protectors as a means of preventing dental trauma. A method of preparing individualized inter-mouth protectors for patients at risk of dental trauma or inclined to suffer trauma is presented. A totally individualized protector is more efficient for the protection and prevention of dental trauma. Two sessions with the patient were required. We conclude that the method was simple, observing all the necessary requirement for this type of device.


Morphologic study of the maxillary molars. Part II: Internal anatomy. The internal anatomy of three hundred and seventy (370) decalcified and cleared human maxillary molars was studied. Seventy-five percent of the first molars, 58% of the second molars and 68% of the third molars studied presented three (3) root canals and 25% of the first molars, 42% of the second molars and 32% of the third molars presented four (4) root canals. The authors observed that the incidence of two root canals in the mesiobuccal root was higher in second maxillary molars than in first maxillary molars.


Odontomas--report of 3 cases.

Odontomas--report of 3 cases. Three clinical cases of odontoma were detected in 2 children and 1 adolescent. The tumors were surgically removed. Clinical suspicion was based on facial deformity in one of the cases and on the absence of permanent tooth eruption in the other two. Radiographic evidence of odontoma was confirmed through histological study.


Risk patterns of Hodgkin's disease in Los Angeles vary by cell type. Over the period 1972-1985, 2729 cases of Hodgkin's disease were diagnosed in Los Angeles County, and 2492 were subclassified using the Rye classification. The occurrence of these cases was examined in relation to age, sex, race, place of birth, social class, occupation, and year of diagnosis. The pattern of nodular sclerosis occurrence conformed to expectations, supporting the polio model of etiology for this subtype. However, the risk pattern of mixed cell disease was quite distinct from that of nodular sclerosis, suggesting that the two may not share a common etiology. The pattern of lymphocyte predominance in Hodgkin's disease, with a special prominence in younger blacks, resembled neither that of nodular sclerosis nor that of mixed cell disease. The cases of lymphocyte-depletion Hodgkin's disease showed no distinctive epidemiological features, and its continued classification with nodular sclerosis and/or mixed cellularity can be justified solely by histological or biological evidence.


The association of diet, obesity, and breast cancer in Hawaii. A case-control study of the association of dietary fat and animal protein consumption with breast cancer was conducted between 1975 and 1980 on Oahu, Hawaii. Data from this study were used to explore the relation of selected foods and the interaction of nutrients and foods with other factors, such as body size, age at menopause, and ethnicity on the risk for breast cancer. The sample included 272 postmenopausal breast cancer cases and 296 neighborhood controls. Study participants included Japanese and Caucasian women, aged 45 to 74, who were residents of Oahu. There was a suggestion of a positive-dose response relation (P < 0.01) between sausage consumption and the odds ratio for breast cancer. Significant odds ratios for breast cancer were also found for higher intakes (above the 50th percentile) of diary items, sausage, and all meats combined. The dose-response relation for nutrients and foods tended to be stronger among women with a high Benn's index (kg/cm1.5182) compared to women with a low Benn's index. In general, subjects with high dietary intakes of fat and animal protein who were in the upper 50th percentile of body size were at the greatest risk for breast cancer. However, there was no evidence for an interaction between the dietary variables and body size, ethnic group, age at menarche, age at menopause, or age at first birth that would affect the odds ratio for breast cancer. These data suggest that women with both a high intake of foods rich in fat and animal protein and with a large body size are at increased risk for breast cancer.


The association of dietary fat with ability to obtain breast fluid by nipple aspiration. The ability to obtain breast fluid by nipple aspiration was examined in relation to self-reported dietary fat intake in 1347 white and 153 black women. Study participants were between 20 and 59 years of age, were not pregnant or breastfeeding, and had no history of breast cancer. The proportion of women from whom nipple aspirate fluid was obtained increased with increasing dietary fat consumption; the odds ratio for obtaining breast fluid was 1.4 (95% confidence interval, 1.0-1.8) in white women who consumed over 90 g of fat/day compared with those who consumed less than 50 g of fat/day, adjusting for age, smoking, and parity. Among black women, the association was much stronger; the odds ratio for obtaining nipple aspirate fluid in those who consumed over 90 g of fat/day was 3.6 (95% confidence interval, 1.3-10.1) compared with those who consumed less than 50 g of fat/day. In both blacks and whites, the associations were most pronounced in women aged 30-44 years. These findings suggest a relationship between dietary fat consumption and breast secretion.


Chromosome rearrangements in fumigant appliers: possible relationship to non-Hodgkin's lymphoma risk. Appliers of pesticides (n = 18) who are exposed to the fumigant phosphine or who have a mixed exposure to other pesticides and phosphine demonstrate a significant increase in chromosome rearrangements in G-banded chromosomes from peripheral blood compared to control subjects (n = 26). Appliers who had discontinued using phosphine for at least 8 months prior to specimen collection (n = 5) do not demonstrate significant increases in chromosome rearrangements compared to controls. Breakpoint analysis of 6,138 metaphases from all subjects demonstrates 196 breaks per 3605 metaphases in exposed subjects and 102 breaks per 2,533 metaphases in control subjects. Bands with significantly more breaks than expected based on band length in all study subjects were 1q32, 3p14, 7p15, and 14q11. Three of these four bands had significantly more breaks than expected in the exposed group, and all four bands had a significant excess of breaks in the control group. There are four bands with a significant excess of breaks in the exposed group and no breaks in the control group; each of these occurs in a known protooncogene region. These are 1p13 (NRAS), 2p23 (NMYC), 14q32 (ELK2), and 21q12 (ETS-2). Most breaks at bands 1p13, 14q32, and 21q22 are associated with chromosome rearrangements and occurred in appliers who have a mixed exposure to phosphine and other pesticides. Cytogenetic abnormalities, i.e., rearrangements and/or deletions involving bands 1p13, 2p23, and 14q32, are associated with non-Hodgkin's lymphoma. We speculate that these findings could relate to the risk of evolution of a neoplastic clone in these workers. Epidemiological studies of similarly exposed workers indicate an excess of non-Hodgkin's lymphoma.


Gastric intestinal metaplasia in ethnic groups in the southwestern United States. The incidence of gastric cancer has declined dramatically in the United States during this century. However, the incidence of gastric cancer among Hispanics, Blacks, and Native Americans remains 2-3-fold higher than among Whites in this country. Populations with an increased risk of gastric cancer have predominantly the "intestinal" type of gastric cancer, and intestinal metaplasia is regarded as a histological precursor lesion of this type of gastric cancer. We sought to establish the prevalence of intestinal metaplasia, identify associated epidemiological factors, and improve detection of this lesion in a patient population undergoing clinically indicated endoscopy in the Southwestern United States. Among the 440 patients studied, we observed an overall crude prevalence of intestinal metaplasia of 19%. However, the crude prevalence among Hispanics and Blacks was found to be markedly higher than among non-Hispanic Whites (50% versus 13%). Two biopsy protocols (two biopsies versus four biopsies) were used during this study, with a significantly higher rate of intestinal metaplasia detection under the four-biopsy protocol. Adjusting for protocol, we found that age and ethnicity were significantly and independently associated with the prevalence of intestinal metaplasia. The odds of intestinal metaplasia diagnosis was significantly higher in Hispanics compared to non-Hispanic Whites (P < 0.001), and the prevalence of intestinal metaplasia increased with advancing age (P = 0.01). The presence of Helicobacter pylori was also significantly associated with the presence of intestinal metaplasia (P = 0.02), although the direction of the association differed between Hispanics and non-Hispanic Whites.


Determinants of plasma ascorbic acid in a healthy male population. The antioxidant properties of vitamin C may be involved in the prevention of cancer. The correlation between dietary vitamin C intake as estimated by a dietary questionnaire and plasma ascorbic acid (AA) was examined in 68 nonsmoking male volunteers aged 30-59 years. Determinants of plasma AA as well as interrelationships between various antioxidants in plasma were also explored. The determinants of plasma AA were examined by a multiple regression model containing dietary vitamin C, calories, body weight, and amount of beverages consumed. Higher vitamin C intake (P < 0.0002) increased plasma AA, while greater body weight (P < 0.005) decreased plasma AA. A significant correlation (r = 0.43; P < 0.0003) between vitamin C intake and plasma AA was observed. There was a negative correlation between plasma AA and plasma uric acid (r = -0.32; P < 0.007) and positive associations between plasma beta-carotene and plasma alpha-tocopherol (r = 0.39; P < 0.001) and between plasma beta-carotene and plasma glutathione peroxidase (r = 0.32; P < 0.008). Vitamin C supplement users had higher plasma AA compared to nonusers. The relationship between plasma AA and vitamin C intake appears to be curvilinear with the non-supplement users at the linear part of the curve and the supplement users at the plateau. Plasma AA is an appropriate biomarker, in our subjects, of dietary vitamin C except for people consuming large amounts of this vitamin either in their diet or in supplemental form.


Evaluation of a test for abnormal rectal mucus for early detection of colon cancer. This report describes the evaluation of a chemical test for T-antigen in rectal mucus as a screening test for colon cancer. The test, called the Mucus Strip Test, detects the disaccharide residue sialic acid-free beta-D-Gal(1-->3)-D-GalNAc or T-antigen, which accumulates in mucus from malignant cells and colonic mucosa adjacent to cancer but not in normal mucosa. Participants were an unselected case series of 660 persons undergoing colonoscopy, excluding those with ulcerative colitis, polyposis, Crohn's disease, or nonspecific inflammatory bowel disease. In the first study (n = 608) rectal mucus was collected after preparation of the bowel for colonoscopy; in the second study (n = 52) a modified protocol was used to collect mucus approximately 2 weeks before colonoscopy and again following preparation for the procedure. Mucus Strip Test results were compared to the diagnosis received after colonoscopy, which was classified as cancer, adenomatous polyp(s), and others (normal). Analyses were also stratified by previous history of large intestinal disease, classified as previous cancer; previous diagnosis of adenomatous polyp(s); or others. In the first study, T-antigen was detected in approximately 30% of mucus samples, and test results were independent of both diagnosis at colonoscopy and previous medical history. In the second study, T-antigen was detected in 85% of samples collected before and 96% of samples collected after preparation for colonoscopy, but test results were again independent of diagnosis and medical history.(ABSTRACT TRUNCATED AT 250 WORDS)


Phospholipid methylation and taurine content of synaptosomes from cerebral cortex of developing rat. Changes in taurine concentration and rate of methylation of phosphatidylethanolamine have been examined in rat brain synaptosomes over the course of development. At 7, 14, 21, 28 and 56 days of age, rats were injected i.p. with 300 microCi/kg [3H-methyl]methionine. Synaptosomes (P2B fraction) were isolated from the cerebral cortex 9 h later and incorporation of the methionine methyl group into phospholipid and protein was investigated. Synaptosomal taurine and methionine concentrations were determined at the same ages, as were the concentrations of the major classes of phospholipids (phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine and phosphatidylserine). Methionine concentration increased between day 7 and 14 and fell thereafter. Phospholipid methylation rates calculated from the specific activity of synaptosomal methionine were high from days 7 and 14 and then fell, whereas protein methionylation increased between day 7 and 28 and then decreased. A strong correlation was found between the taurine concentration of the synaptosome and phospholipid methylation rates during brain development. Protein methionylation rates, however, showed no correlation with taurine concentration.


Isolation and characterization of two benzene-derived hemoglobin adducts in vivo in rats. The present study was aimed at the characterization of the major adducts formed by reaction of the metabolites of [14C]benzene with rat hemoglobin in vivo. Groups of 12-week-old male Fisher rats received i.p. injections of a single dose of 10 mmol/kg body weight or three equal daily subdoses of 3.3 mmol/kg body weight of [14C]benzene. High-performance liquid chromatographic analysis of strong acid hydrolysates of the [14C]benzene-modified globin indicated that the two major adducts in rats cochromatographed with synthetic S-(2,5-dihydroxyphenyl)cysteine and S-phenylcysteine. These adducts were converted to O,O'-S-tris-acetyl-3-thiol-hydroquinone and S-phenylthioacetate, which were then characterized by gas chromatography/mass spectrometry. The major radioactive adduct peaks accounted for 60-75% of the total radioactivity associated with rat globin. Characterization of the S-(2,5-dihydroxyphenyl)cysteine adduct provides evidence that p-benzoquinone is formed as a reactive metabolite of benzene. Formation of the S-phenylcysteine adduct indicates that benzene oxide and/or a hydroxycyclohexadienyl free radical is formed as an active intermediate upon i.p. injection of benzene into rats.


Regulatory role of a neurotransmitter (5-HT) on glial Na+/K(+)-ATPase in the rat brain. In the present work we studied the effect of serotonin (5-HT) on the kinetics of Na+/K(+)-ATPase in subcellular preparations of the cerebral cortex from male Wistar rats using various concentrations of ATP and K+ with and without added 5-HT. Also we studied the effect of 5-HT on the enzyme in glial or neuronal preparations. The results indicated that there was a significant increase (P < 0.05) of the Vmax in the presence of 5-HT in the whole tissue preparation (homogenate) but not in the subcellular fractions, suggesting that the interaction could be preferentially with the glial pump. Further results supported that this was the case since activation by 5-HT was mainly in the glial preparations. Kinetic data and the binding of [3H]ouabain supported that the enzyme is activated by 5-HT through the exposure of more enzymatic active sites.


Glial cells in coculture can increase the acetylcholinesterase activity in human brain endothelial cells. The elements of the cholinergic system (acetylcholinesterase and choline acetyltransferase) and butyrylcholinesterase were studied in human cortical capillary samples, brain-derived endothelial cell cultures and glial cell cultures. It was shown that the elements of the cholinergic system are present in the microvessels, but the choline acetyltransferase activity may be due to contamination with cholinergic nerve terminals since no choline acetyltransferase could be demonstrated in endothelial cell cultures. The present results revealed that the activity of acetylcholinesterase is reduced in the cortical endothelial cell cultures after longer culture times, while butyrylcholinesterase activity is not altered. In a system where endothelial cells were cocultured with embryonic human brain astroglial cells for 12 days in vitro, the acetylcholinesterase activity was increased 2-fold. These results support a glial influence on the enzyme activity of the cerebral endothelium.


Isolation and characterization of hamster brain polyribosome-cytomatrix complexes. We have developed a method for the isolation of a brain subcellular fraction enriched in both highly aggregated polyribosomes and cytoskeletal proteins. This method is based on gentle dispersion of brain tissue and low speed centrifugation. This fraction is enriched in typical cytoskeletal proteins as glial fibrillary protein, neurofilament proteins and actin. Messenger RNA did not seem to be involved in the polyribosome association to the cytomatrix as shown by the effect of exposure to micrococcal nuclease. On the other hand, in vivo disruption of protein synthesis by acute experimental phenylketonuria, hypothermia or heat-shock did not cause the release of ribosomes from the cytomatrix.


Patients' perceptions on participation in a cancer chemoprevention trial. The perceptions of patients regarding the benefits, disadvantages, and importance of their participation in a long-term cancer chemoprevention trial, the Isotretinoin-Basal Cell Carcinoma Prevention Trial, were assessed through a questionnaire mailed at the conclusion of the 3-year treatment period of the trial. Responses were evaluated overall, as well as within subgroups defined by sex, age, education level, treatment group, presence of side effects, and the number of skin biopsies performed during the 3-year intervention phase. Overall, "careful medical follow-up received" (43%) and "being part of a research effort" (24%) were the most frequently cited important benefits, while the "amount of time taken to attend clinic" (32%) and "side effects" (20%) were the most frequently cited unpleasant aspects of trial participation. Most surveyed patients viewed the study as "very or extremely important" to their general health (62%) and their skin cancer condition (88%) and, as a result of participation, felt "much or somewhat better" physically (52%). The majority indicated that they would "definitely or probably" be willing to take part in another research study (79%) and take the study medication, if it were shown to be effective in the trial (78%). Overall and subgroup data provide important insights into patient motivations and attitudes regarding cancer chemoprevention trial participation, adherence, and satisfaction.


In vitro neurotransmitter release in an animal model of depression. Sprague-Dawley rats exposed to uncontrollable shock can be separated by a subsequent shock escape test into two groups: a "helpless" (LH) group which demonstrates a deficit in escape behavior, and a "nonlearned helpless" (NLH) group which shows no escape deficit and acquires the escape response as readily as naive control rats (NC) do. The present studies were designed to examine the correlations between the behavioral differences and the changes of in vitro neurotransmitter release seen in these three groups of rats. The major finding concerned a significant increase in endogenous and K(+)-stimulated serotonin (5-HT) release in the hippocampal slices of LH rats. There were no apparent differences in acetylcholine, dopamine and noradrenaline release in the hippocampus of LH rats as compared to NLH and NC rats. These results add further support to previous studies in our laboratory which implicate presynaptic 5-HT mechanisms in the behavioral deficit caused by uncontrollable shock.


Increased cardiac production of dihydroxyphenylalanine (DOPA) during sympathetic stimulation in anaesthetized dogs. Entry of dihydroxyphenylalanine (DOPA) into plasma from specific organs may reflect regional activity of tyrosine hydroxylase, the enzyme responsible for the immediate synthesis of DOPA and rate-limiting for subsequent formation of catecholamines. Therefore, cardiac spillovers of DOPA, noradrenaline and the intraneuronal metabolite of noradrenaline, dihydroxyphenylglycol (DHPG), were examined during two periods of graded electrical stimulation of the sympathetic nerves to the heart in anesthetized dogs. Responses were examined before and after neuronal uptake blockade with desipramine. Cardiac spillover of DOPA increased by 1.8- and 4.4-fold during sympathetic stimulation before desipramine and by 1.6- and 3.3-fold after desipramine. Fold increases in cardiac spillover of DOPA were much lower than but positively related with fold increases in noradrenaline spillover (5.9- and 13.8-fold increases before and 9.0- and 15.8-fold increases after desipramine). Increases in cardiac spillover of DHPG (1.5- and 2.3-fold increases) were blocked by desipramine so that fold changes in spillover of DOPA were greater than and poorly related to changes in spillover of DHPG. Fold increases in cardiac spillover of DOPA showed a close one-to-one positive relationship with fold increases in the sum of cardiac spillovers of noradrenaline and dihydroxyphenylglycol before and after desipramine. For a given fold increase in noradrenaline release, transmitter turnover is increased fractionally and noradrenaline synthesis need also only increase fractionally to maintain transmitter stores constant. The close relationship between fold increases in cardiac spillover of DOPA and combined spillovers of noradrenaline and DHPG is consistent with regulation of tyrosine hydroxylase activity to match changes in noradrenaline synthesis with changes in noradrenaline turnover. Changes in cardiac spillover of DOPA appear to reflect local changes in tyrosine hydroxylase activity.


[Leu31-Pro34] neuropeptide Y identifies a subtype of 125I-labeled peptide YY binding sites in the rat brain. Subtypes of the neuropeptide Y (NPY) receptor in the rat brain were identified by the use of the selective Y-1 analog, [Leu34-Pro34] NPY. In rat brain homogenate binding studies, [Leu31-Pro34] NPY was found to produce a partial inhibition of 100 pM 125I-labeled peptide YY (PYY) binding with a plateau at 50-1000 nM [Leu31-Pro34] NPY resulting in a 70% inhibition of binding. The C-terminal fragment NPY 13-36, a putative Y-2 agonist, exhibited very little selectivity in rat brain homogenates. Scatchard analysis of 125I-labeled PYY binding to rat brain homogenate yielded biphasic plots with Kd values of 40 and 610 pM. Inclusion of 100 nM [Leu31-Pro34] NPY was found to eliminate the low affinity component of 125I-labeled PYY binding leaving a single, high affinity binding site with a Kd of 68 pM. In autoradiographic studies, displacement curves indicated that [Leu31-Pro34] NPY completely inhibited binding in the cerebral cortex with little effect on the binding in the hypothalamus. On the other hand NPY 13-36 inhibited binding in the hypothalamus at low concentrations but required higher concentrations to inhibit binding in the cerebral cortex. Other brain regions such as the hippocampus, appeared to contain both subtypes. Subsequent to these studies, a quantitative autoradiographic map was conducted using 50-100 pM 125I-labeled PYY in the presence and absence of [Leu31-Pro34] NPY which produced a selective displacement of binding in certain distinct brain regions. These areas included the cerebral cortex, certain thalamic nuclei and brainstem while ligand binding was retained in other brain regions including the zona lateralis of the substantia nigra, lateral septum, nucleus of the solitary tract and the hippocampus. Numerous brain regions appeared to contain both receptor subtypes. Therefore, the Y-1 and Y-2 receptor subtypes exhibited a somewhat distinct distribution in the brain. In addition, 125I-labeled PYY appears to label the Y-2 receptor with relatively higher affinity when compared to the Y-1 receptor.


A pharmacological comparison of [3H]GBR12935 binding to rodent striatal and kidney homogenates: binding to dopamine transporters? Binding of [3H]GBR12935 to homogenates of mouse and rat striatum and kidney was studied. [3H]GBR12935 bound to both tissue preparations with high affinity (mouse striatum Kd = 2.4 +/- 0.4 nM, n = 4; mouse kidney Kd = 3.8 +/- 0.9 nM, n = 4), in a saturable (striatal Bmax = 1.5 +/- 0.4 pmol/mg protein; kidney Bmax = 4.9 +/- 0.5 pmol/mg protein) and reversible manner. Saturation experiments revealed the presence of a single class of high affinity binding sites in both tissues of both species. Mouse kidney appeared to possess a greater density of [3H]GBR12935 binding sites than the striatum while the reverse situation prevailed for the rat. Although two dopamine uptake inhibitors, namely GBR12909 and benztropine, displaced [3H]GBR12935 binding from striatal and kidney homogenates with a similar affinity in both tissues of these species, unlabelled mazindol, (+/-)cocaine, nomifensine and amfonelic acid were significantly (P < 0.001-0.02) more potent inhibitors of [3H]GBR12935 binding in the striatum than in the kidney. While the pharmacological profile of [3H]GBR12935 binding in the rodent striatum compared well with that of the dopamine transporter reported previously, the pharmacology in the kidney was considerably different to that in the striatum. GBR12909 (1-30 mg/kg, i.p.), a close analog of GBR12935, induced significant antidiuretic and antinatriuretic effects in spontaneously hypertensive rats. These data suggest that while [3H]GBR12935 labels the dopamine uptake sites in the brain, it does not appear to label similar sites in the kidney. The mechanism of action of GBR12909 on sodium and water excretion remains to be determined.


Fluorescence digital image analysis of thrombin and ADP induced rise in intracellular Ca2+ concentration of single blood platelets. Cytoplasmic free Ca2+ concentration, [Ca2+]i, was estimated in single rabbit blood platelets by digital imaging microscopy with the use of the specific Ca(2+)-indicator dye Fura-2. Uneven distribution and low level of [Ca2+]i was found in the resting platelet even in the presence of extracellular 1 mM Ca2+. Thrombin at 1 unit/ml immediately caused a transient increase in [Ca2+]i, which was followed by a secondary and sustained increase in [Ca2+]i. The distribution of increased levels of [Ca2+]i was also shown to be uneven within the cell. The presence of 1 mM EGTA in the medium only slightly decreased the initial rise in [Ca2+]i, but completely inhibited the latter phase, a sustained rise in [Ca2+]i. This result shows that the initial rise of [Ca2+]i might not be caused by Ca2+ influx, but might be induced by mobilization of Ca2+ from intracellular Ca2+ storage sites. This speculation is further supported by the fact that the elevated [Ca2+]i induced by thrombin immediately decreased to the base line value when 3 mM EGTA was applied. Thus, thrombin induced elevation of [Ca2+]i is suggested to consist of two different processes, namely the mobilization of Ca2+ from the intracellular storage sites and the successive Ca2+ influx through the receptor activated Ca2+ channels. Stimulation with ADP also caused a rapid elevation of platelet [Ca2+]i, but this effect of ADP was different form that of thrombin. Thus, the ADP induced rise in [Ca2+]i was accompanied by oscillation and was inhibited by extracellular EGTA. Our present experiment is the first report that clearly and directly reveals the differences between the effects of thrombin and ADP on [Ca2+]i of platelets.


Effect of N,N'-dicyclohexylcarbodiimide on the binding of vesamicol, an inhibitor of acetylcholine transport into synaptic vesicles. Vesamicol is a highly potent inhibitor of active acetylcholine transport into isolated cholinergic vesicles from Torpedo. On the basis of transport kinetics and vesamicol sensitivity, we have shown that the acetylcholine transporter could be in an activated state even in the absence of a stimulated ATPase. In this preparation, N,N'-dicyclohexylcarbodiimide (DCCD), an hydrophobic carbodiimide, inactivates both ACh transport and vesamicol binding. Inhibition of vesamicol binding by DCCD is time dependent, saturable and prevented by vesamicol. DCCD first affected the affinity constant for vesamicol. Ki-value for DCCD lies in the micromolar range. These results imply that there is a DCCD reactive site within the ACh transporter and that it is located in an hydrophobic environment near the vesamicol binding site. SDS-gel electrophoresis after labelling of the vesicle membrane proteins with [14C]DCCD shows that radioactivity is mainly incorporated in a 15 kDa subunit. Time-course and concentration dependence of [14C]DCCD labelling and vesamicol inhibition do not coincide. Hence, the two processes are probably unrelated and the result rather points to another inactivation mechanism which can be an intramolecular cross link.


Different effects of L-, N- and T-type calcium channel blockers on striatal dopamine release measured by microdialysis in freely moving rats. Using a microdialysis method, we have investigated effects of the voltage-dependent calcium channel blockers, verapamil, nicardipine, omega-conotoxin and flunarizine on the dopamine release and metabolism in the striatum of freely moving rat. Perfusion of verapamil (1-300 microM) and nicardipine (1-100 microM), an L-type calcium channel blocker, into the striatum through the dialysis membrane showed a dose-dependent decrease of dopamine release in the dialysate and slight increase of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Treatment of omega-conotoxin (0.1, 1 microM), an N-type channel blocker, decreased about 50% basal dopamine release and slightly decreased DOPAC and HVA levels. Treatment with flunarizine (10 microM), an T-type channel blocker, did not affect the dopamine release and metabolism. From these data, it appears that treatments of the L- and N-type voltage-dependent calcium channel blockers in rat striatum suppress basal dopamine release, but T-type blocker does not suppress it, suggesting that L-, N- and T-type calcium channels regulate in vivo dopamine release in a different mechanism.


Secretion of peptidylglycine alpha-amidating monooxygenase (PAM) from rat salivary glands. Peptidylglycine alpha-amidating monooxygenase (PAM) is a regulating enzyme to synthesize the biologically active hormones having carboxy-terminal amide. In the present study we investigated secretion of the enzyme from rat saliva. Property of PAM in the saliva was similar to that in the submandibular gland. Both enzymes showed similar pH optimum at 5.0 and optimal ascorbic acid concentration at 2.5 mM. But molecular size of PAM in the saliva was 75 kDa in the gel permeation chromatography on Superose 12 column, while the size in the submandibular gland was 25 kDa. After the treatment with trypsin, PAM in the saliva was converted to a small size molecule, which is similar to the size in rat submandibular gland. These and other data indicate that a native molecular size of PAM is secreted into saliva and plays some physiological roles.


Molecular characterization of D2 dopamine-like receptors from brain and from the pituitary gland. D2 dopamine-like receptors have been purified from five bovine brain regions (caudate nucleus, putamen, olfactory tubercle, frontal cortex, cerebellum) and the anterior and neurointermediate lobes of the pituitary gland using a combined ligand-affinity and lectin-affinity chromatography procedure. In all the brain regions except cerebellum and in the neurointermediate lobe of the pituitary gland the purified species appeared as a M(r) 95,000 doublet on SDS-PAGE. In the anterior lobe of the pituitary an additional M(r) 142,000-145,000 species was seen. The M(r) 95,000 species had a low affinity for the lectin wheat germ agglutinin (WGA) whereas the M(r) 142,000-145,000 species had a higher affinity for WGA and additionally showed some affinity for concanavalin A. It is concluded that both the M(r) 95,000 and 142,000-145,000 species are D2 dopamine-like receptors and that the differences between the species are mainly at the oligosaccharide level. Some evidence was also obtained for heterogeneity at the protein level which may correspond to the D2(short) and D2(long) isoforms of these receptors.


Myelin isolation: comparison of sedimentation and flotation techniques. Brains from young (20 day old) and adult rats were used to compare myelin yields obtained by sedimentation and flotation techniques. The flotation method consistently gave approx 70% higher yields of myelin than the sedimentation method. Both myelin preparations have virtually identical protein composition as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electrophoretic analysis revealed substantial concentrations of myelin proteins in the non-myelin particulate fraction obtained by the sedimentation but not by the flotation method. The study indicates that the paradigm of the sedimentation method results in a significant loss of myelin during isolation, and that this loss can be avoided or minimized by employing the flotation method.


Nonenzymatic incorporation of glucose and galactose into brain cytoskeletal proteins in vitro. Initial studies demonstrated the loss of lysine and simultaneous appearance of glucitollysine in intracellular proteins following incubation with sugar. For example, when a crude nervous tissue cytoskeletal preparation was incubated in 100 mM glucose for 10 days, > 60% of the lysine residues were modified. Over 20% of the lysyl residues in a spinal cord neurofilament preparation are susceptible to Schiff base formation after one day and over 30% following five days of incubation with 100 mM glucose. When incubated with 100 mM galactose, F- and G-actin were found to be significantly modified in as few as 15 h, with > 70% of the lysyl residues lost. After 45 h of incubation, > 90% of the residues had been modified. These data also indicate that many of the lysyl residues in F- and G-actin are exposed and very susceptible to modification by sugar. This rapid and extensive modification of lysine in actin in vitro suggest that it may be modified in diabetic nervous tissue.


Identification of glucocorticoid responsive elements (GREs) at far upstream of rat NPY gene. The location of three glucocorticoid responsive elements (GREs) in rat neuropeptide Y (NPY) gene was determined by chloramphenicol acetyltransferase (CAT) assay and nucleotide sequencing. We have reported that mRNA content of rat prepro-NPY is increased by 1.7-fold in NG108-15 cells by 1 microM dexamethasone, suggesting the presence of GRE in the gene. To identify the element, the 5'-flanking DNA of 3.3 kilobases (kb) was isolated from rat NPY gene. When chimeric chloramphenicol CAT plasmids containing various deletions of the NPY upstream sequence were transfected into NG108-15 cells, the region between -2.9 and -2.1 kb relative to the cap site was found to potentiate the transcription of CAT gene in the presence of 1 microM dexamethasone. The nucleotide sequencing of this region revealed three GRE consensus sequences at -2.5, -2.2 and -2.1 kb. The results indicate that these elements present in the far upstream region of the NPY gene confer induction by glucocorticoids.


Decreased prostaglandin synthesis in postmortem cerebral cortex from patients with Alzheimer's disease. The syntheses of prostaglandin (PG) F2 alpha, E2 and D2, and thromboxane (TX) B2 from [14C]arachidonic acid were studied in frontal cortex of human control and Alzheimer's disease (AD) brains using the microsomal fractions. Under the assay conditions employed, it was found that the major metabolite of [14C]arachidonic acid was PGE2 accounting for 63% of total prostanoid production; PGF2 alpha accounted for 21.5%, TXB2 for 9%, and PGD2 for 6.5%. When AD samples were compared to control samples, microsomal PG synthesis was significantly decreased, with reduced production of PGE2, PGF2 alpha and PGD2. Such decreases in AD brain seem unrelated to age, sex, postmortem delay and, as far as could be determined, antemortem state. In both control and Alzheimer groups, a history of anti-inflammatory therapy seemed to correlate with increased PG synthesis.


[35S]t-butylbicyclophosphorothionate binding sites in susceptible and cyclodiene-resistant houseflies. 4-aminobutyric acid (GABA)-gated chloride ion channels are important molecular targets for a number of polychlorocycloalkane compounds including cyclodiene insecticides. Previous radioligand binding studies have indicated that cyclodiene insecticides are potent inhibitors of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to housefly thorax and abdomen membranes. In the present study, a laboratory-reared, cyclodiene-resistant (CYW) housefly strain (Musca domestica) showed resistance to a number of cyclodiene insecticides. Specific, saturable [35S]TBPS binding was detected in thorax and abdomen membranes prepared from housefly strains susceptible (CSMA) and resistant (CYW) to cyclodienes. Scatchard analysis of [35S]TBPS binding data from CSMA and CYW membranes revealed no significant differences between the two strains in either the affinity (Kd) or the density (Bmax) of specific, saturable binding sites. There were no differences in the comparative effectiveness of a range of polychlorocycloalkanes, including cyclodiene insecticides, as inhibitors of specific [35S]TBPS binding to CSMA and CYW thorax and abdomen membranes. Therefore, if an alteration in target site is a mechanism for resistance to cyclodienes in the CYW strain, it is not readily measurable using [35S]TBPS.


Rat brain fatty acid-binding protein during development. Cytosolic fatty acid-binding proteins (FABPs) have been described in rat and bovine whole brain. In the present study we investigated the distribution of FABP among white matter and gray matter as well as its changes during development. Fatty acid binding activity was similar in white and gray matter up to 40 days of age. In white matter it showed an age dependent increase thereafter, while in gray matter it remained constant throughout. Gel filtration (Sephadex G-75) of white matter cytosol of adult female rats resolved the fatty acid-binding activity in two peaks: A (Vo) and B (12-14 KDa; FABP). The specific binding activity in the FABP fraction was 10.4 pmol/micrograms of protein. The activity in peak A showed an age-dependent increase which paralleled myelin deposition. In contrast, the activity in the FABP fraction (peak B) remained undetectable up to 40 days of age, increasing thereafter. The differential distribution of cellular brain proteins with the capacity to bind fatty acids in gray matter and white matter suggests that this activity could be related to glial cells or to cell related structures such as myelin.


How much undernourishment is required to retard brain myelin development. This study employs a large population of developing rats designed to range continuously from above a normal, average weight to severely undernourished. The purpose of the study is to determine if brain myelin development is vulnerable to mild growth retardation from chronic hunger, or if brain myelin development is altered only after a certain tolerable amount of growth retardation is exceeded. The brains were examined at a landmark age, weaning, since myelination is one of the most vulnerable features of brain development and its rate of synthesis is highest at this age. Brain size was logarithmically related to body weight, and brain growth retardation increased as the severity of food deprivation increased. There was an additional reduction in the concentration of brain myelin. In contrast to brain weight, the reduction in myelin concentration was linearly related to body size over the full range from well nourished to undernourished. From a population perspective, these data indicate growth retardation from undernourishment in any amount slows brain growth and additionally lowers the concentration of brain myelin; however, individuals, in both well nourished and undernourished groups, vary widely. Implications and cautions of extrapolation to human populations are discussed.


Expression of cloned aromatic L-amino acid decarboxylase in Xenopus laevis oocytes. Sense mRNA coding for bovine adrenal medulla aromatic L-amino acid decarboxylase (AADC) was expressed following microinjection into Xenopus laevis oocytes. The expressed enzyme activity was stereoselective for L-5-hydroxytryptophan and L-DOPA and blocked by NSD-1015 an inhibitor of AADC. Heating the expressed enzyme at 55 degrees C resulted in a parallel loss of activity towards both substrates. Our findings are consistent with the prevailing notion that a single enzyme is able to decarboxylate both substrates in vivo.


Development modulates the serum induced effect on the incorporation of [2-3H]mannose into chick optic lobe protein: the possible role of glia. Recently, we described that serum decreases tritiated mannose incorporation into protein in the chick optic lobe at 18 days of embryonic age (Rossi et al., 1990). In this paper, we found a strikingly different response of this serum effect according to age. The data obtained showed no serum induced decrease in 6-10-day-old embryo. In addition, our results demonstrate that the differential response of the tissue to the serum is independent of the rate of sugar entry into nerve cells. Furthermore, we also report that the variation of mannose or leucine incorporation into protein coincides very closely with the pattern of protein and glycoprotein accumulation during chick optic lobe development. Finally, data were obtained to define glial cells as the cellular target of the serum induced effect. This finding may contribute to elucidate the mechanism of cellular pathogenesis of cerebral lesions that occur after the breakdown of the blood brain barrier, such as in some diseases or during bleeding after injuries.


Phospholipid composition of oligodendroglial cells during normal development and in 18 day old hyperthyroid and malnourished rats. The phospholipid composition of isolated oligodendroglial cell perikarya was studied in normal rats during development and in 18 day old malnourished and hyperthyroid rats. Phosphatidyl choline and phosphatidyl ethanolamine were found to be the major phospholipid constituents of oligodendroglial cells. Phospholipid content increased during development, mainly due to an increase of the above mentioned phospholipids. The major changes were observed in sphingomyelin, phosphatidyl serine, phosphatidyl inositol and phosphatidyl ethanolamine between 18 and 30 days of age. The phospholipid and protein content per cell was significantly decreased in the oligodendroglial cells isolated from malnourished rats as compared to controls. When data were expressed as a function of total proteins, the composition was similar to that of normal animals. In the hyperthyroid rats on the other hand, there were no changes in the amount of phospholipids per cell, while phospholipids per milligram of total oligodendroglial cell protein were markedly decreased. The changes in myelin composition produced by hyperthyroidism that we have previously described, do not follow closely those produced by this experimental condition in oligodendroglial cells, suggesting that the metabolism of myelin might be to a certain extent, independent of that in the parent cell.


Muscarinic cholinergic receptor binding in rat hindlimb somatosensory cortex following partial deafferentation by sciatic nerve transection. Peripheral nerve injury or amputation leads to extensive changes within the central representations of the mammalian body surface. The mechanisms responsible for post-traumatic reorganization of these maps in adults may also, at least partly, underlie a more general feature of the somatosensory system--the capacity for stimulus-dependent plasticity. Acetylcholine has been implicated in both of these processes. We studied the binding of the ligands [3H]QNB and [3H]pirenzepine in rat hindlimb somatosensory cortex from 1 to 14 days following sciatic nerve transection. Although the [3H]QNB binding was not different from normal levels in tissue homogenates of the affected somatosensory cortex, differences were demonstrated when binding was measured on a layer-by-layer basis. [3H]QNB binding was changed only in certain layers, at certain times. The predominant effects appeared to be a decrease in binding in the middle layers from 4 to 14 days after the transection. Combining the [3H]QNB data with data obtained from the more M1-selective ligand [3H]pirenzepine suggested that complex changes occur among several muscarinic receptors, including receptors with non-M1 subtype characteristics. Moreover, unilateral nerve transection affects the hindlimb somatosensory regions in both hemispheres.


Memantine stimulates inositol phosphates production in neurones and nullifies N-methyl-D-aspartate-induced destruction of retinal neurones. Whereas carbachol, noradrenaline, serotonin and memantine stimulated inositol phosphates production and calcium mobilization in 3-5 day old rabbit retinal cultures, only carbachol and noradrenaline were effective when 25-30 day old cultures were used. The older retinal cultures contain only Müller cells which shows that the memantine and serotonin effects on the 3-5 day old cultures are specifically associated with neurones. While the carbachol, noradrenaline and serotonin effects were respectively blocked by atropine, prazosin and ketanserin, none of these substances influenced the memantine responses. In all areas of the rat brain which were analysed, the effectiveness of memantine, noradrenaline and carbachol on the stimulation of inositol phosphates production was similar. However, in the rabbit retina, as opposed to the rat brain slices, carbachol had a more pronounced influence than noradrenaline in stimulating inositol phosphates production. Chick retina exposed to N-methyl-D-aspartate, quisqualate, glutamate or kainic acid resulted in cytopathological damage to cell bodies in the outer nuclear layer. The N-methyl-D-aspartate effect was nullified by memantine and MK-801 but not by kynurenic acid. In contrast the kainic acid-induced damage was specifically antagonized by kynurenic acid. The present results show that memantine influences the metabolism of inositol phosphates in neurones but not glial (Müller) cells and appears to counteract the N-methyl-D-aspartate induced cytopathological damage. How these two effects of memantine are interrelated and whether they are involved in the described beneficial therapeutic observations of memantine (as in dementia) remains to be established.


Passive avoidance learning in the young chick results in time- and locus-specific elevations of alpha-tubulin immunoreactivity. A monoclonal antibody was used to examine changes in immunoreactivity of the cytoskeletal protein, alpha-tubulin, following passive avoidance learning in day-old chicks. Postmitochondrial fractions (16,000 g supernatants) were prepared from specific forebrain loci taken at several time points after training and assayed with the anti-alpha-tubulin antibody, YL1/2. Of the regions examined, elevations in the titre of YL1/2 were found in the left intermediate hyperstriatum ventrale 1 h, 6 h and 24 h following training, in the left lobus parolfactorius 1 h following training and in the right lobus parolfactorius 6 h and 24 h following training. No training-related changes were detected in a third forebrain region, the paleostriatum augmentatum. These results regarding the cellular dynamics of memory formation in the chick confirm and expand on earlier findings from our laboratory.