Control of mosquito larvae in the port city of Assab by an indigenous larvivorous fish, Aphanius dispar. A randomized controlled trial was carried out in Assab under the auspices of the National Organization for the Control of Malaria and other Vectorborne Diseases of Ethiopia to assess the effectiveness of an indigenous cyprinodontid fish, Aphanius dispar, in controlling mosquito larvae, including the local malaria vector, Anopheles culicifacies adanensis. Cisterns, wells and barrels were found to be important breeding sites for the malaria vector and for culicine mosquitoes. Fish were equally effective in controlling mosquito larvae in all the types of breeding site investigated. The overall proportion of sites with fish that harboured mosquito larvae was 1.6%, ranging from 1.5 to 1.7% according to type of site, as compared to 34% in sites left unstocked, ranging from 17.9 to 60.0%. Monthly restocking of fish where necessary was found to be sufficient to maintain an adequate level of control. Stocking of larvivorous fish in wells and household water storage containers was well-accepted by the participants, who were aware of the role of the fish in malaria prevention and found the fish useful in keeping their water free of other aquatic organisms. Based on the results of this study, larvivorous fish were introduced on an operational scale for the control of malaria transmission in Assab, with the voluntary participation of the population and the collaboration of the Municipality and health authorities of Assab.


Malaria entomological inoculation rates in western Venezuela. Over 61,000 anophelines collected between January 1988 and October 1989 in three villages in western Venezuela were assayed by ELISA for Plasmodium vivax circumsporozoite (CS) protein. The six specimens confirmed positive belonged to three species: Anopheles (Nyssorhynchus) nuneztovari Gabaldón, 1940, A. albitarsis Arribalzaga, 1878 sensu lato and A. oswaldoi (Peryassu, 1922). The estimated CS protein rate for all species combined was 0.01% (95% confidence limits 0.004-0.02%). This CS protein rate and the mean number of bites received by the collectors indicated a sporozoite inoculation rate of about 10.5 infective bites per person per year. From this value and the number of human malaria cases reported it was estimated that only 0.32% of bites by CS-positive mosquitoes led to a malaria infection. The CS protein rate is so low that this parameter would not be a practical indicator of the efficacy of control campaigns in this area.


Evolution of the retrotransposons TRS/ingi and of the tubulin genes in trypanosomes. The African trypanosomes have genomes of high plasticity, as demonstrated for instance by their ability to shuffle their genes around, coding for variant-specific surface glycoproteins (VSGs). Another indication of their genome plasticity is the presence of multiple retro-elements. The retrotransposon-like element TRS/ingi is present in many copies in the genome of trypanosomes. One particular derivative of TRS/ingi, called TUBIS, had previously been found to interrupt a tubulin gene in a particular strain of T. brucei. Here both TRS/ingi and TUBIS were studied by hybridizing genomic DNA of various strains and species of trypanosomes with suitable probes in order to elucidate the evolution of this family of retro-elements. The TSR/ingi elements are highly repeated and have very long open reading frames, while TUBIS clearly is a truncated, inactivated form of this element, found in only one particular chromosomal location. Both elements were shown to be present in several strains and species of the subgenus Trypanozoon, in particular in T. brucei brucei, T. gambiense, T. rhodesiense, T. equiperdum and T. evansi. They could not be detected in species of other subgenera, in particular in T. congolense and T. cruzi. These findings suggest that the retrotransposon TRS/ingi was acquired by trypanosomes only after divergence of present day subgenera. The TUBIS element was found in exactly the same chromosomal location (at the 3' end of the tubulin gene cluster) in many different strains and species of the subgenus Trypanozoon. This shows that the element was transposed to this location before speciation of the subgenus. Although, TRS/ingi is unlikely to be involved directly in VSG switching, it may have contributed to the genome plasticity of trypanosomes.


Demographic findings relevant for health care planning and evaluation collected through a malaria control project in the Kivu Mountains, Zaire. Population studies were conducted in the margin of a community based malaria control programme in the Katana Health zone, in the Eastern part of Zaire. The reported findings are based on prospective registration of vital events from March 1986 through February 1987. At mid term 28.083 people were covered. The age and sex structure of the population was typical for tropical Africa, apart from an excess of males to females after the age of 64. The mean age at marriage was 21.2 years for women and 25.6 years for men. 89% of women did not complete a single year of formal education. The crude fertility rate was 250/1000 and total fertility 8.3 children. The infant mortality rate and the child mortality quotients attained 130/1000 and 183/1000 respectively. The crude death rate was 23 per 1000 and the natural population growth rate 31/1000. Due to a net out-migration of 28/1000 the zone's population remained, however, virtually stable. The latter observation questions the purported role of demographic pressure as a key determinant of the region's slow socio-economic development. The other findings provide valuable baseline and background information for planning and evaluating health-related activities.


Distribution and severity of onchocerciasis in southern Benin, Ghana and Togo. The Onchocerciasis Control Programme in West Africa has recently extended its operation in southern Benin, Ghana and Togo. To estimate the number of people infected and blinded by onchocerciasis and to describe the distribution and severity of the disease in the extension area, 99 villages were selected, using a stratified random sampling procedure, and surveyed. All the ecological and entomological information available was used in the sampling procedure and in the selection of 87 non-representative villages surveyed to confirm the findings. The study estimated that 590,468 people are infected and 11,715 blind from onchocerciasis out of a rural population of 1,878,234. The Pru, Asukawkaw and Mono river basins were areas with high risk of onchocercal blindness. The Oueme and Zou river basins in Benin and the mountainous areas between Ghana and Togo were classified as areas with medium risk of onchocercal blindness. The other parts of the study area presented low or no risk of onchocercal blindness. By detecting the river basins where villagers are at risk of onchocercal disease this study permits the selection of populations for disease control based on mass distribution of ivermectin, a microfilaricide.


Factors affecting morbidity and mortality on-farm and on-station in the Ethiopian highland sheep. Factors affecting morbidity and mortality of the Ethiopian highland sheep were studied both on-farm and on-station at Debre Berhan between 1989 and 1990. Primary causes of infectious origin resulted in high proportional morbidity (88.4% on-farm) and mortality (72.9% on-farm and 71.8% on-station) rates. Nutritional and managemental factors were also responsible for mortalities in lambs. The most frequent secondary causes of morbidity and/or mortality were ectoparasites and nasal myiasis. Health management interventions on-station were not high enough to produce performance improvements above the on-farm levels. However, the occurrence of gastrointestinal parasites significantly (P < 0.05) differed between the two management systems. The frequency of some of the major causes of morbidity and mortality such as pneumonia, fasciolasis and enteritis were significantly (P < 0.01) affected by season and age of an animal. In order to alleviate the major health constraints identified in this study, a proper health management intervention involving vaccination, strategic anthelmintic treatment and feeding management are suggested.


The development of manifest psoriatic lesions is linked with the invasion of CD8 + T cells and CD11c + macrophages into the epidermis. Koebner response was studied in 35 psoriatic patients. Two punch biopsies per patient were taken from non-lesional psoriatic skin before, and 6 h, 2 days, 7 days, 14 days and 21 days after, tape stripping. Alterations in the numbers of CD1+ Langerhans cells, CD4+ and CD8+ T cells and CD11c+ macrophages were mapped morphometrically. Results were compared with lesional and non-lesional psoriatic skin, and control skin. Nine of 35 patients were Koebner-positive. No statistically significant differences were noted between non-lesional psoriatic and control skin. CD4+ T cells increased in number 2 days after trauma in both the epidermis and the dermis, whereas epidermal CD8+ T cells and CD11c+ macrophages increased only in the Koebner-positive lesional skin after 7 days. The changes in lesions induced by tape-stripping resembled those seen in lesional psoriatic skin (mature plaques). The number of CD1+ cells increased in mature psoriatic lesions only. It seems possible that trauma per se stimulates the accumulation of CD4+ T cells at the site of injury, but the development of manifest psoriatic lesions correlates with invasion of CD8+ T cells and CD11c+ macrophages into the epidermis.


Effect of inorganic phosphate on hypoxanthine transport in isolated brain microvessels. In isolated brain microvessels, used as an in vitro model of the blood-brain barrier, the rate of hypoxanthine uptake was modulated by the presence of inorganic phosphate. A single high-capacity, low-affinity transport system was apparently active in a phosphate-free medium (Vmax = 840 pmol/mg protein/min, Km = 750/uM); in the presence of 10 mM phosphate, there was also a low-capacity, high-affinity system (Vmax = 47 pmol/mg protein/min, Km = 27/uM). The phosphate-dependent component was inactive in the absence of glucose or of Na+ ions, or upon addition of phloretine (but was scarcely affected by 2,4-dinitrophenol). This activity was apparently coupled to the intracellular phosphoribosyltransferase-catalyzed conversion of purines into the corresponding nucleotides: when inorganic phosphate was present in the suspending medium, labeled hypoxanthine was transported with higher efficiency and was readily converted to inosine monophosphate and to other related nucleotides. In the absence of phosphate ions, hypoxanthine was instead metabolized to xanthine and uric acid.


Fractionation of gamma-glutamyl transpeptidase from the rat brain, kidney and pancreas by concanavalin A affinity chromatography. gamma-Glutamyl transpeptidase (GGT) in tissue extracts from five brain regions, the kidney and pancreas of 50-day-old rats was examined for its specific activity and affinity to immobilized concanavalin A (Con A). According to their descending GGT activity, the tissue extracts were classified in the following order: kidney >> pancreas >> olfactory bulbs > medulla oblongata > hippocampus > cerebellum > frontal cortex. Using different concentrations of methyl-alpha-D-mannopyranoside for the elution of GGT from Con A-Sepharose column, the enzyme from brain regions could be separated into five fractions, two of which contained about 75% of the total GGT activity without regional differences in elution profiles. Almost complete GGT activity in kidney tissue extracts was eluted in a single peak whereas the enzyme from pancreas exhibited two peaks.


Beneficial effects of befunolol on post-hypoxic recovery of cardiac contractility and myocardial metabolism. The present study was undertaken to determine whether befunolol (BFE 60, CAS 39543-79-8) a beta-adrenoceptor blocking agent, improves post-hypoxic contractile and metabolic recovery of perfused hearts. Isolated rat hearts were perfused for 20 min under hypoxic conditions, followed by 45-min reoxygenation. Hypoxia/reoxygenation induced less than 5% post-hypoxic recovery of cardiac contractile force, incomplete return of resting tension of hearts, accumulation of tissue calcium, and release of purine nucleosides and bases, and creatine kinase from the heart. When hypoxic hearts were treated with 500 mumol/l befunolol from 0 to 10 min of hypoxic perfusion, marked recovery of contractile force (more than 50% of the pre-hypoxic value), complete suppression of the tissue calcium accumulation and significant suppression of the increase in creatine kinase activity of the perfusate were seen after reoxygenation. This treatment also significantly prevented the release of purine nucleosides and bases during hypoxia. These results suggest that treatment with befunolol during hypoxic perfusion is beneficial for post-hypoxic recovery of cardiac function and myocardial metabolism, probably through a mechanism of suppression of transmembrane flux of substrates, ions and enzymes. Cardiac contractile force upon the onset of hypoxia declined more rapidly and myocardial high-energy phosphate content after 10 min of hypoxia was significantly higher in befunolol-treated hearts than in hearts without treatment. Thus, energy-sparing effects may also contribute to the beneficial post-hypoxic recovery of cardiac function and metabolism.


Relative bioavailability of carbinoxamine and phenylpropanolamine from a retard suspension after single dose administration in healthy subjects. The plasma pharmacokinetics of carbinoxamine (CA, CAS 486-16-8) and phenylpropanolamine (PP, CAS 14838-15-4) after single dose administration of a retard suspension (Rhinopront), containing a resinate as sustained-release agent, were compared to those of the same active principles given as an aqueous solution. The study was performed in 20 healthy subjects who received the two formulations according to a standard crossover design with a one-week wash-out. Blood samples were obtained up to 24 h post-dose. PP and CA were assayed in the plasma samples by gas chromatography with electron-capture detection and HPLC with coulometric detection, respectively. The pharmacokinetic results indicated sustained release of the two active principles with the retard suspension: CA appeared in plasma at a much slower rate than with the solution, a 30% lower Cmax being reached after 8.0 h instead of 3.0 h post-dose. For PP, Cmax was 23% lower and occurred 3.0 post-dose instead of 1.5 h with the solution. The extent of absorption of the two drugs, as assessed by AUC (0-24 h), was slightly smaller with the retard suspension than with the aqueous solution. However, the test/reference ratio remained within 95% confidence intervals of 80-87% and 88-98% for CA and PP, respectively, indicating bioequivalence of the two formulations. A simulation of the plasma levels during repeated administration indicated that dosing with the retard suspension at 12-h intervals should yield the same steady-state plasma levels as a 5 times daily administration of a divided dose of the aqueous solution, for both drugs.


Pharmacological treatment of allergies.

Pharmacological treatment of allergies. According to recent literature, the "anti-allergy" properties of antihistamines are linked to their antagonistic ability on receptor H1. In the majority of experimental models the immediate allergic responses is followed by a late phase. Especially at the pulmonary level, the presence of a late response after an allergic provocation is considered to correlate with the severity of asthma. The reference anti-allergy drugs, such as the inhaled corticosteroids or the cromones, without anti H1 activity, inhibit this late pulmonary response. Azelastine, ketotifen and cetirizine, three substances that are antagonistic to the anti-H1 receptor reduce the late pulmonary response. In addition, these three substances have other "anti-allergy" characteristics. Azelastine inhibits production of superoxide by the pulmonary neutrophils and eosinophils after PAF provocation in animals. Cetirizine significantly inhibits eosinophil infiltration in the bronchoalveolar lavage liquid in asthmatics with a late allergic bronchospasm. The presence of anti-histaminic and anti-allergy characteristics on the same molecule may perhaps convey a supplementary therapeutic benefit in the treatment of allergic symptoms.


[The mediator mechanisms of the ventral hippocampus in anxiety states formed by different aversive exposures]. Microinjections of monoamines and amino acids into rat ventral hippocampus showed functional relevance of GABA- or dopamine- and 5-HT-ergic mechanisms of this structure of brain formed by aversive actions of diverse biological importance rather than glutamate-ergic ones. The participation of hippocampus monoamine- and acidergic mechanisms in the origin of diverse aversive anxiety is discussed.


[The ultrastructural characteristics of the endocrine cells of the normal murine cecum and in experimental escherichiosis]. Ultrastructural investigations and a quantitative analysis of caecum endocrine cells were performed in the period from 15 minutes to 2 weeks after inoculation, using the model of experimental escherichiosis. The authors identified 5 types of endocrinocytes in the caecum of mice and showed the reaction of these cells: degranulation, extrusion of granules and their accumulation dependent on the time of the exposure.


SDZ PSC-833--a novel potent in vitro chemosensitizer in multiple myeloma. Multiple myeloma cell lines and patient tumor samples with and without the expression of the classical multidrug resistance (MDR) phenotype were investigated in vitro for drug induced cytotoxicity and modulation of drug resistance. Overall there was a good correlation in the cell lines between MDR expression, as measured by immunocytochemistry with monoclonal antibodies against P-glycoprotein 170 (Pgp), and in vitro resistance to doxorubicin (dox) and vincristin (vcr). Drug resistance in the cell line RPMI 8226 dox 40, expressing a high level of Pgp, was almost completely reversed by the novel non-immunosuppressive cyclosporin A (CsA) analog SDZ PSC-833 (PSC), while the chemosensitizers verapamil, CsA and quinine, in clinically achievable concentrations, were much less effective. In cell lines with low Pgp expression, PSC and the other chemosensitizers seem equally effective. The patient tumor samples were selected to represent different combinations of Pgp expression, drug resistance and effects of chemosensitizers. PSC and CsA appeared equally potent and resistance modulation was detected not only in Pgp positive, but also in Pgp negative tumor samples. Furthermore, in one case of a Pgp expression myeloma, chemosensitizers were without effect. These findings indicate the need to incorporate in vitro chemosensitivity assays with Pgp determination when the effects of MDR modulating chemosensitizers are to be studied in the clinic.


The effect of estrous cycle and buthionine sulfoximine on glutathione release from the in vitro perfused rat ovary. There is little known regarding the intracellular mechanisms of modification of damage in the ovary. Ovarian perfusion of en block dissections of the rat right ovary with aorta and vena cava were done to determine (a) if glutathione (GSH) is released by the ovary, (b) if the release is cycle dependent, and (c) if GSH released is the product of de novo ovarian synthesis. All perfused ovaries released GSH and the release was maximal at estrus and least at metestrus. Perfusion with buthionine sulfoximine, a specific inhibitor of gamma-glutamylcysteine synthetase, resulted in a dose-dependent reduction in GSH released, indicating inhibition of de novo synthesis during perfusion.


Occurrence of nasopharyngeal carcinoma in aboriginals of Taiwan: report of 14 cases. The authors describe the rare occurrence of nasopharyngeal carcinoma (NPC) in 14 aboriginals of Taiwan (ABT), a minor ethnic group now accounting for less than 2% of the total population in Taiwan. The observation is epidemiologically unusual, representing a low-risk ethnic group in an NPC prevalent area. With regard to patient characteristics, symptomatology and pathology, we have not found any appreciable differences in reports from other geographic areas. Serological profiles of antiEBV-VCA (Epstein-Barr virus, viral capsid antigen) antibody in 7/9 patients available for review of IgA and 5/7 patients available for review of IgG were found significantly elevated, ranging respectively from 1:40-640/1:160-1280. Interestingly, 12 of the 14 patients were found to be exclusively from the Paiwan tribe residing in Pintung, a district in southern Taiwan. Since the exact prevalence of NPC in this minority remains unknown, it is not clear whether the apparent preponderance is real or merely causal due in part to geographic bias. To a lesser extent, however, our observations indicate that NPC is not an uncommon malignancy in Paiwan aboriginals of southern Taiwan.


Lobar bronchioloalveolar carcinoma: an ultrasound study. To assess whether chest ultrasound (US) can be useful in the diagnosis of lobar bronchioloalveolar carcinoma, we retrospectively analyzed the US patterns of eight patients with bronchioloalveolar carcinoma presenting with lobar consolidation. For comparison, 15 patients with lobar consolidation of a benign etiology were also analyzed. We found that the US patterns of lobar bronchioloalveolar carcinoma had a characteristic homogeneous, echogenic pattern. The air-bronchograms and air-alveolograms were scarce when compared to benign consolidation. The sensitivity of using these US criteria in discriminating lobar bronchioloalveolar carcinoma was 75%, and the specificity was 93%. We also assessed the yield of US-guided transthoracic cutting biopsies in the diagnosis of lobar bronchioloalveolar carcinoma. The diagnostic rate of the US-guided cutting biopsy was 100%, which was superior to other diagnostic procedures, such as sputum cytology (37%), fiberoptic bronchoscopy with brushing or biopsy (32%) and trans-thoracic needle aspiration cytology (50%). None of the patients developed complications. We conclude that the distinct US pattern for lobar bronchioloalveolar carcinoma is a helpful diagnostic sign, and the US-guided biopsy is a useful approach in the diagnosis of lobar bronchioloalveolar carcinoma.


Therapeutic effect of carbon dioxide laser versus single application of trichloroacetic acid for koilocytic squamous papillae. This paper reports the treatment results of 50 symptomatic females who had clinical features of squamous papillae and histologic evidence of koilocytosis. Either a carbon dioxide laser or a single application of trichloroacetic acid (TCA) was used to treat these patients. All of the patients were alternately and prospectively randomized into one of two groups. Twenty-three of the 25 women treated by laser and 10 of the 25 women treated by TCA had resolution of either the symptoms or the vulvar lesions in a follow-up period ranging from six to 22 months. Hence, we were able to control the symptoms and lesions in 92% of the women following initial laser treatment and 40% of the women following a single application of TCA. In addition, cosmetic results were satisfactory, and complications were minimal in the laser-treated group of patients. However, human papillomavirus DNA was still detected three to four weeks after treatment in 24% of the women treated by laser and 64% of the women treated by TCA. Whether they are at a higher risk of recurrence as compared to those without detectable viral DNA remains to be determined.


Loop excision for cervical intraepithelial neoplasia. We report the results of a prospective trial using a loop electrosurgical excision procedure (LEEP) on 97 patients with cervical intraepithelial neoplasia. In the LEEP group the mean cutting time and whole procedure time were 6.2 +/- 1.9 seconds and 12.7 +/- 3.5 minutes, respectively. The average blood loss was 3.6 +/- 1.9 mL. In the control group (39 cases) using laser conization, the mean cutting time and whole procedure time were 11.7 +/- 3.5 minutes and 44.9 +/- 8.9 minutes, respectively. The average blood loss in the control group was 11.2 +/- 3.1 mL. The differences between the two groups were statistically significant. During LEEP surgery, four cases had accidental vaginal excision. There were three cases of late cervical bleeding after surgery; the surface of the cervix was smooth, and no adhesion or crypt formation was noted after re-epithelialization. Eight patients became pregnant after the loop excision and no cervical incompetence was noted during antenatal care. After a one-year follow-up period in the colposcopy clinic, there was no recurrence of cervical intraepithelial neoplasia in either group. We advise that among the modalities of treatment for cervical intraepithelial neoplasia, LEEP appears to offer patients several benefits such as less bleeding, precise specimens, local anesthesia, less cost and less discomfort. It is particularly suitable for treating younger women who have not yet completed their families.


Effect of external load on isokinetic torque production by the knee in anterior cruciate ligament deficient patients. The purpose of this study was to examine the effect of an external load on the isokinetic torque production of the knee directly from the anterior cruciate ligament (ACL) of deficient patients. Ten surgically proven ACL deficient patients were included in this study. Each patient was preoperatively studied using a Biodex isokinetic dynamometer. Isokinetic contraction of the quadriceps muscle and hamstring muscles were performed in five repetitions with an angular velocity of 45 degrees per second with proximal and distal pad placement, respectively. The results demonstrated that the ratio of torque production of the ACL deficient knee to the contralateral normal knee was greater in proximal pad placement than in distal placement and that the ratio of torque production of the knee in proximal pad placement to that of the knee in distal pad placement was greater in the ACL deficient knee than in the contralateral normal knee. Similar results were found for both extension and flexion of the knee. The results showed that ACL deficient patients felt more confident doing isokinetic contractions of the knee with proximal pad placement.


Treatment of osseous defects with fibroblast-coated hydroxylapatite particles. Several techniques of periodontal regeneration have been used, including hydroxylapatite (HA) grafting, demineralized free-dried bone allografts and guided tissue membranes, for which clinical merits still need further scientific study. The purpose of this pilot study was to examine the healing of periodontal defects using HA grafts coated with fibroblasts isolated from the periodontal ligament (PDL). We cultured fibroblast-like cells either from a clinically healthy site of the PDL or gingival tissues of the subject receiving the cell transplantation. We added HA to the cultures and allowed the cells to migrate onto the HA surface. Then the HA particles coated with cells were harvested and transplanted into the periodontal osseous defects of four patients after phase I treatment. Three HA grafts without coating cells were used as controls. Periapical x-ray and clinical parameters were monitored for up to six months. Scanning electron microscopy demonstrated that fibroblast-like cells had proliferated on the HA particles in vitro. Our results showed that the experimental group had greater pocket reduction and clinical attachment gain, and less gingival recession than did the control group at six months postoperatively. Periapical films revealed good filling of osseous defects in both groups. This study introduces a new biological approach for bringing PDL cells into intimate contact with root surfaces, in order to facilitate earlier repopulation of root surfaces with regenerative PDL cells.


Reactivity of anti-mitochondrial antibodies in primary biliary cirrhosis and systemic sclerosis. Anti-mitochondrial antibodies (AMA) were detected by indirect immunofluorescence in the sera of 16 out of 17 (94%) patients with primary biliary cirrhosis (PBC). Immunoblotting experiments with mitochondrial polypeptides from the porcine liver as antigens revealed that three antigens were recognized by the sera from AMA-positive patients. These were a 70-kD protein recognized by nine out of 16 AMA-positive sera, a 50-kD protein recognized by 13 out of 16 AMA-positive sera and a 39-kD protein recognized by four out of 16 AMA-positive sera. The reactivity of these polypeptides was destroyed by brief exposure to trypsin. None of these antigens were recognized by any of the 30 control sera. These results show that the 70-kD, 50-kD and 39-kD proteins are the major mitochondrial autoantigens recognized by sera from patients with PBC. In addition, of 30 sera samples from patients with diffuse scleroderma, 13 reacted to the 70-kD and/or 50-kD antigens. Anti-centromere antibodies (ACA) were also detected in the sera of five of the 17 (29%) patients with PBC. The high prevalence of ACA in patients with PBC and the presence of anti-70- and 50-kD antibodies in patients with diffuse scleroderma provide evidence of an association between these two disorders.


Rapid prenatal determination of fetal sex by polymerase chain reaction on amniocyte DNA. Sex determination in early gestation is important for fetuses at risk for X-linked disorders or congenital adrenal hyperplasia. One hundred and seventy consecutive samples of amniocytes were collected between the 12th and 31st gestational week. Seven women received early amniocentesis before the 14th week. Fetal sex was determined by amplification of Y-specific DNA fragments within five hours. All results of the polymerase chain reaction, except for one false-negative, were compatible with cytogenetic analyses. Polymerase chain reaction of amniocyte DNA provides a rapid technique for sex determination in early gestation with high specificity and sensitivity.


Coronary artery bypass surgery utilizing right gastroepiploic artery. Fifteen patients (10 men, 5 women), who underwent coronary artery bypass surgery utilizing the right gastroepiploic artery (R't GEAR) in combination with either the left internal mammary artery (LIMA) or the greater saphenous vein as graft material, were studied. The reasons for utilizing R't GEAR were previous coronary artery bypass operations with resulting marked wound adhesion prohibiting LIMA harvest (five cases), LIMA jeopardized during surgery (three cases), total arterial revascularization using LIMA + R't GEAR (four cases), and near total arterial revascularization using LIMA + R't GEAR + saphenous veins (SV) (three cases). A total of 40 coronary arteries were revascularized: the R't GEAR was used for revascularization of 11 left anterior descending arteries, three right coronary arteries, and one left circumflex artery; LIMA was used for revascularization of four left anterior descending arteries, and three diagonal arteries; the saphenous vein was used for revascularization of eight left circumflex arteries, three diagonal arteries, six posterior descending arteries, and one proximal right coronary artery. There were no hospital mortalities, and follow-up studies revealed satisfactory early results. From our preliminary experience with these 15 cases, we assume that the R't GEAR can be used as the graft material of choice for coronary artery bypass in cases where difficulty in LIMA utilization is encountered or insufficient vein graft conduit is available. It is particularly valuable in reoperations for coronary arterial disease.


Open heart surgery in geriatric patients. With the progress of medical science, the scope of open heart surgery has expanded. From 1975 through 1987, we operated on 114 consecutive patients aged 65 years and over with the aid of a cardiopulmonary bypass in the Department of Surgery, National Taiwan University Hospital. The annual number of these elderly patients has increased gradually, reaching 6.4% of the annual open heart cases in 1987. Eighty-six of our 114 patients were males and 28 were females. Their ages ranged from 65 to 88 years with an average of 68.5 years. Overall, 65 patients (57%) were operated on for coronary artery disease and/or its associated lesions; 41 (36%), for valvular heart disease; six, for aortic dissection; two, for cardiac tumor; and one, for congenital pulmonary stenosis. One patient had combined coronary artery disease and aortic dissection. The mortality for isolated coronary artery bypass surgery was 12%; for single valvular surgery it was 11%. The complexity of the surgical procedure increased the operative mortality. The overall mortality was 23.6% (27/114), with subsequent death in 5.7% during an average of 25 months of follow-up. Because of the degeneration of organ-systems in elderly patients, and its frequent association with poor cardiac reserve and other medical problems, these elderly cardiac patients should be checked thoroughly before they are considered for open heart surgery. Our experience suggests that open heart surgery can be done in selected patients aged 65 years or older with acceptable risks. Age alone should not be an absolute contraindication to surgery, and clinical improvement is to be expected after surgery.


Exercise thallium-201 tomographic scintigraphy in the diagnosis of coronary artery disease: emphasis on the effect of exercise level. Exercise thallium-201 imaging using single-photon emission computed tomography (SPECT) was evaluated in 154 patients with angiographically documented coronary artery disease (CAD) and in 25 normal subjects. Of the 154 patients with CAD, 134 (87%) had abnormal thallium images. By contrast, only 77 (50%) patients had ischemic ST-segment depression (p < 0.001). Among 25 normal subjects, 20 had normal exercise SPECT images. The specificity of exercise SPECT imaging (80% or 20/25) in excluding patients with CAD was not significantly higher than that of exercise electrocardiography (76% or 19/25). For the detection of individual vessel involvement by analysis of territories of perfusion abnormalities, the sensitivity and specificity of exercise SPECT were 72% and 96% for the left anterior descending, 78% and 85% for the right coronary, and 47% and 98% for the left circumflex artery. Ninety (group 1) of the 154 patients with CAD achieved adequate exercise end points (ischemic ST-segment depression or > 85% of maximal predicted heart rate) and 64 (group 2) did not. Exercise SPECT showed significantly more perfusion abnormalities in group 1 than in group 2 (96% vs 75%, p < 0.001). We conclude that: (1) exercise SPECT thallium imaging is more sensitive than exercise electrocardiography for detecting patients with CAD; (2) the sensitivity of the test is affected by the level of exercise; and (3) it is valuable in the identification of individual vessel involvement.


Angiodysplasia as a source of intestinal bleeding: report of seven cases. From October 1978 to April 1991, seven patients presenting at the National Taiwan University Hospital with gastrointestinal tract hemorrhage were diagnosed by colonofibroscopy or angiography as having angiodysplasia of the colon and small intestine. There were two men and five women; their ages ranged from 23 to 65 years, with a mean age of 50.3 years. None of these patients were diagnosed by barium enema. Only two patients were diagnosed by colonofibroscopy, and six patients were diagnosed by angiography. Therefore, angiography was the most effective method for diagnosing angiodysplasia. A vascular tuft was the most frequent finding. Six patients with lesions on the right side of the colon underwent a right hemicolectomy, one patient with a lesion on the jejunum underwent a right hemicolectomy initially with segmental resection of the jejunum later. The postoperative courses were smooth, and there has been no further evidence of gastrointestinal blood loss or anemia in the follow-up period. A right hemicolectomy is the treatment of choice because these lesions are frequently multiple; the lesions are found primarily on the right side of the colon.


Mosaic ring chromosome 13 analyzed by fluorescence in situ hybridization: report of a case. A five-year-old boy with psychomotor retardation, microcephaly, bilateral cataracts, hearing impairment and hypospadia with microphallus was found to have multiple cell lines from peripheral blood: 46,XY/46,XY, -13,+r(13)/46, Xy, -13, +dic r(13) in the ratio of 35%/61%/4% by trypsin-Giemsa, and C-bandings. Using fluorescence in situ hybridization (FISH) with biotin-labeled alpha-satellite probe (D21Z1/D13Z1) and fluorescence staining (FITC), we confirmed that the ring originated from chromosome 13. To elucidate changes in the chromosome ends in the ring originated from chromosome 13. To elucidate changes in the chromosome ends in the ring formation, we used human telomere-specific probes for FISH study; it showed an absence of telomeres on the ring chromosome, although Ag-NOR staining was positive. These findings yielded different breaking points on the ends of both the short and long arms of chromosome 13 from those reported in the literature.


Herpes esophagitis: a cause of upper gastrointestinal bleeding in an immunocompetent patient. Herpes esophagitis presents as dysphagia and odynophagia in the majority of cases. Rarely has hematemesis been reported. We report a case of herpes esophagitis presenting with hematemesis in an immunocompetent patient. This 67-year-old man suffered from herpes esophagitis, proven by a panendoscopic examination, with characteristic histological findings. He presented with hematemesis and passage of tarry stools, but was otherwise healthy with normal humoral, cell-mediated immunity and was negative for human immunodeficiency virus antibody. Only supportive treatment was given. He has been well for the past nine months since the initial diagnosis.


Early diagnosis of a vein of Galen aneurysm: report of a case. Congenital vascular malformation with an aneurysm of the vein of Galen is rarely seen, particularly in the prenatal period. With the advancement of diagnostic techniques such as ultrasonography, we were able to detect a case prenatally and to diagnose it postnatally.


[Identification of a de novo mutation in a factor FVIII:C gene in a family requesting prenatal diagnosis of hemophilia A]. Hemophilia is caused by wide spectrum of different mutations in the F8C gene which made the direct DNA diagnosis of the diseases not the case of choice. Indirect DNA diagnosis by means of linked restriction fragment length polymorphisms (RFLPs) provides the alternative. Using this method authors identified de novo mutation in a family requiring prenatal diagnosis of hemophilia A. This de novo mutation arose during the spermatogenesis of the proband's father. Attempts to characterize the mutation on the molecular level are presented. (Ref. 15, Fig. 1.).


[The effect of glycoside Tripterygium wilfordii Hook F on the immune regulatory function of T lymphocyte]. Previously, we treated successfully patients with systemic lupus erythromatosus (SLE) with glycoside Tripterygium Wilfordii Hook F, a Chinese medicinal herb. To evaluate the pharmacological mechanism of this herb, we studied its effects on the activation and proliferation facets of human T lymphocyte in vitro. The results revealed that this drug can markedly suppress the activation and proliferation facets of T lymphocytes.


[Leptotrombidium scutellare in transmission of epidemic hemorrhagic fever virus]. To further elucidate the role of Leptotrombidium scutellare in transmission of epidemic hemorrhagic fever virus (EHFV), a series of studies were carried out from 1988 to 1990. EHFV was isolated from both larvae of free mites collected from the grassland of endemic areas and larvae of filial mites hatched in the laboratory. The suckling mice bitten by these larvae were infected by EHFV. Because only the larvae of chigger mite can bite vertebrate hosts and only take a full meal in its entire life cycle, the pathogen carried by it can only be originated from its parent mite via transovarial route. Thus it can be confirmed that the natural infection of EHFV in these mites is transferred via transovarial transmission. The results demonstrate that L (L.) scutellare can naturally be infected by EHFV; EHFV can be transmitted to the vertebrate host by biting of the larvae and can be transferred via transovarial transmission in mites; and therefore, L (L.) scutellare can serve as a transmitting vector of EHF.


A comparison of fentanyl, esmolol, and their combination for blunting the haemodynamic responses during rapid-sequence induction. The purpose of this randomized, double-blind study was to compare the ability of a combination of fentanyl and esmolol to blunt the haemodynamic effects of intubation with that of either agent alone. Patients received fentanyl or saline four minutes before, and esmolol or saline two minutes before rapid-sequence induction of anaesthesia. The F2 group (n = 24) received fentanyl 2 micrograms.kg-1, the E2 group (n = 24) received esmolol 2 mg.kg-1, the F2/E2 group (n = 25) received a combination of fentanyl 2 micrograms.kg-1 and esmolol 2 mg.kg-1, and the F5 group (n = 26) received fentanyl 5 micrograms.kg-1. Following tracheal intubation, the maximum percent change from baseline heart rate was less in the F2/E2 and F5 groups (12% and 16% respectively) than in the E2 group (34%)(P < 0.05). The maximum percent changes from baseline systolic blood pressure in the F2/E2 and F5 groups (15% and 6% respectively) were less than in the F2 and E2 groups (24% and 33% respectively) (P < 0.05). The combination of a low dose of fentanyl and esmolol provides an alternative to a higher dose of fentanyl for blunting the haemodynamic responses to laryngoscopy and tracheal intubation during rapid-sequence induction in healthy patients.


Anaesthetic management of a parturient with myocardial infarction related to cocaine use. Cocaine abuse is common among parturients with an incidence of 11.8 to 20%. Myocardial infarction is a rare and lethal event during pregnancy with an incidence of 1 in 10,000 pregnancies. We present the anaesthetic management of a parturient of 36 wk gestation who suffered a myocardial infarction nine hours before delivery which was temporally related to "crack" cocaine use. The patient's cardiovascular system became unstable following cocaine use, and she required mechanical ventilatory support and pharmacologic stabilization guided by invasive haemodynamic monitoring. This patient survived a non-Q wave myocardial infarction, but the prognosis of peripartum myocardial infarction remains poor with a mortality rate of 30-40% which is increased if the infarction occurs in the third trimester or postpartum period. The optimal mode and timing of delivery after myocardial infarction is unresolved. The association between cocaine use and myocardial infarction was first described in 1982, and cocaine remains unique among local anaesthetics in its ability to compromise the cardiovascular system through both sympathomimetic effects and vasoconstrictive effects on coronary arteries. Because of the prevalence of substance abuse, cocaine use should be considered in the differential diagnosis of sudden cardiovascular compromise in parturients.


Correlation of proliferative index (PCNA reactivity and Ki-67 reactivity) in primary breast carcinoma with hormone status, lymph node status, and disease-free survival. The proliferative activity in 42 cases of breast cancer were assessed immunohistochemically using antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67. These indices were correlated with the steroid receptor status, pathologic stage, and disease-free survival. There was a strong direct correlation between the two proliferation indices (r = .902, P < 0.001, Kendall's rank correlation). There was a weak correlation between the hormone receptor status and proliferation indices that was not significant when statistically tested. The cases were stratified into PCNA low proliferative index (PI) group (< 4.5% positive cells) and PCNA high PI group (> 4.5% positive cells). In the low PI group, five of 18 (28%) patients were node-positive in contrast to eight of 14 (58%) patients in the high PI group. After a follow-up period of 42-60 months, 14 of 19 (74%) patients in the low PI group were disease-free compared to 10 of 17 (53%) patients in the high PI group. The PCNA and Ki-67 proliferative indices appear to be of great prognostic value and may help identify a subset of breast cancer patients who should be given adjuvant therapy.


MIS (Multicentric Isradipine Study of antihypertensive therapy). One-year open Multicentric Isradipine Study (MIS) performed in 7 centres in Czechoslovakia included 144 patients with mild and moderate hypertension. Isradipine was given at a dose of 2.5 mg daily. If normalization of diastolic blood pressure (BP) had not been reached, the dosage was increased to 5 mg. Monotherapy with isradipine normalized diastolic BP in 44% of patients. Isradipine (5 mg daily) was combined with bopindolol in patients in whom isradipine alone failed to normalize diastolic BP. These had higher mean systolic and diastolic BP, body weight, erythrocyte and platelet counts at the beginning of the study. The combination of isradipine with bopindolol normalized diastolic BP in 87% of the group at the end of 48 weeks' treatment. Tolerance was excellent in 82% of patients. Treatment was discontinued in 8% patients, undesirable effects being the reason in 2%, ineffective therapy in 2% and poor adherence to therapy in 4%. Isradipine in monotherapy or in combination with bopindolol did not exert an adverse effect on the metabolic risk factors of ischaemic heart disease (cholesterol, glycaemia).


Ultrabithorax is a regulator of beta 3 tubulin expression in the Drosophila visceral mesoderm. beta 3 tubulin expression accompanies the specification and differentiation of the Drosophila mesoderm. The genetic programs involved in these processes are largely unknown. Our previous studies on the regulation of the beta 3 tubulin gene have shown that upstream sequences guide the expression in the somatic musculature, while regulatory elements in the first intron are necessary for expression in the visceral musculature. To further analyse this mode of regulation, which reflects an early embryonic specification program, we undertook a more detailed analysis of the regulatory capabilities of the intron. The results reveal not only a certain degree of redundancy in the cis-acting elements, which act at different developmental stages in the same mesodermal derivatives, but they also demonstrate in the visceral mesoderm, which forms a continuous epithelium along the body axis of the embryo, an early action of regulators guiding gene expression along the anterior-posterior axis of the embryo: an enhancer element in the intron leads to expression in a subdomain restricted along the anterior-posterior axis. This pattern is altered in mutants in the homeotic gene Ultrabithorax (Ubx), whereas ectopic Ubx expression leads to activity of the enhancer in the entire visceral mesoderm. So this element is likely to be a target of homeotic genes, which would define the beta 3 tubulin gene as a realisator gene under the control of selector genes.


An amphioxus homeobox gene: sequence conservation, spatial expression during development and insights into vertebrate evolution. The embryology of amphioxus has much in common with vertebrate embryology, reflecting a close phylogenetic relationship between the two groups. Amphioxus embryology is simpler in several key respects, however, including a lack of pronounced craniofacial morphogenesis. To gain an insight into the molecular changes that accompanied the evolution of vertebrate embryology, and into the relationship between the amphioxus and vertebrate body plans, we have undertaken the first molecular level investigation of amphioxus embryonic development. We report the cloning, complete DNA sequence determination, sequence analysis and expression analysis of an amphioxus homeobox gene, AmphiHox3, evolutionarily homologous to the third-most 3' paralogous group of mammalian Hox genes. Sequence comparison to a mammalian homologue, mouse Hox-2.7 (HoxB3), reveals several stretches of amino acid conservation within the deduced protein sequences. Whole mount in situ hybridization reveals localized expression of AmphiHox3 in the posterior mesoderm (but not in the somites), and region-specific expression in the dorsal nerve cord, of amphioxus neurulae, later embryos and larvae. The anterior limit to expression in the nerve cord is at the level of the four/five somite boundary at the neurula stage, and stabilises to just anterior to the first nerve cord pigment spot to form. Comparison to the anterior expression boundary of mouse Hox-2.7 (HoxB3) and related genes suggests that the vertebrate brain is homologous to an extensive region of the amphioxus nerve cord that contains the cerebral vesicle (a region at the extreme rostral tip) and extends posterior to somite four.(ABSTRACT TRUNCATED AT 250 WORDS)


Lox2, a putative leech segment identity gene, is expressed in the same segmental domain in different stem cell lineages. The segmented tissues of the adult leech arise from a set of five, bilaterally paired embryonic stem cells via a stereotyped sequence of cell lineage. Individual segments exhibit unique patterns of cell differentiation, and previous studies have suggested that each stem cell lineage establishes at least some aspects of its own segmental specificity autonomously. In this paper, we describe a putative leech segment identity gene, Lox2, and examine its expression in the various stem cell lineages. Both sequence analysis and the segmental pattern of Lox2 expression suggest a specific homology to the fruitfly segment identity genes Ubx and abdA. In situ hybridization reveals a cellular accumulation of Lox2 RNA over a contiguous domain of 16 midbody segments (M6-M21), including postmitotic neurons, muscles and the differentiating genitalia. Lox2 transcripts were not detected at the stage when segment identities are first established, suggesting that Lox2 gene products may not be part of the initial specification process. Individual stem cell lineages were labeled by intracellular injection of fluorescent tracers, and single cell colocalization of lineage tracer and hybridization reaction product revealed expression of Lox2 RNA in the progeny of four different stem cells. The segmental domain of Lox2 RNA was very similar in the various stem cell lineages, despite the fact that some stem cells generate one founder cell/segment, whereas other stem cells generate two founder cells/segment.


Expression patterns of vHNF1 and HNF1 homeoproteins in early postimplantation embryos suggest distinct and sequential developmental roles. The homeoproteins HNF1 (LFB1/HNF1-A) and vHNF1 (LFB3/HNF1 beta) interact with an essential control element of a group of liver-specific genes. During development, these putative target genes are initially expressed in the visceral endoderm of the yolk sac and subsequently in fetal liver. To assess the possible involvement of HNF1 and/or vHNF1 as transcriptional regulators in the early steps of visceral endoderm differentiation, we have analyzed the expression pattern of both factors both in vitro during differentiation of murine F9 embryonal carcinoma cells and in vivo during early postimplantation mouse development. We show here that differentiation of F9 cells into either visceral or parietal endoderm is accompanied by a sharp induction in vHNF1 mRNA and protein. By contrast, only low levels of aberrantly sized HNF1 transcripts, but not DNA-binding protein, are found in F9 cells and its differentiated derivatives. At 6-7.5 days of gestation, high levels of vHNF1 mRNA are present in the visceral extraembryonic endoderm, which co-localize with transcripts of the transthyretin gene. HNF1 transcripts are first detected in the yolk sac roughly two embryonic days later, after the developmental onset of transcription of target genes. As development proceeds, discrepancies are observed between the level of transcripts of both vHNF1 and HNF1 and their respective nuclear binding proteins, notably in the yolk sac and embryonic kidney. In addition, we show that two alternative spliced isoforms of vHNF1 mRNA, vHNF-A and vHNF1-B, are expressed in both embryonic and adult tissues. Taken together, these data suggest that vHNF1 participates as a regulatory factor in the initial transcriptional activation of the target genes in the visceral endoderm of the yolk sac, whereas the later appearance of HNF1 could be required for maintenance of their expression. Our results also provide evidence of a posttranscriptional level of control of vHNF1 and HNF1 gene expression during development, in addition to the spatial restriction in transcription.


Maintenance of the engrailed expression pattern by Polycomb group genes in Drosophila. The stable maintenance of expression patterns of homeotic genes depends on the function of a number of negative trans-regulators, termed the Polycomb (Pc) group of genes. We have examined the pattern of expression of the Drosophila segment polarity gene, engrailed (en), in embryos mutant for several different members of the Pc group. Here we report that embryos mutant for two or more Pc group genes show strong ectopic en expression, while only weak derepression of en occurs in embryos mutant for a single Pc group gene. This derepression is independent of two known activators of en expression: en itself and wingless. Additionally, in contrast to the strong ectopic expression of homeotic genes observed in extra sex combs- (esc-) mutant embryos, the en expression pattern is nearly normal in esc- embryos. This suggests that the esc gene product functions in a pathway independent of the other genes in the group. The data indicate that the same group of genes is required for stable restriction of en expression to a striped pattern and for the restriction of expression of homeotic genes along the anterior-posterior axis, and support a global role for the Pc group genes in stable repression of activity of developmental selector genes.


Apical ridge dependent and independent mesodermal domains of GHox-7 and GHox-8 expression in chick limb buds. The homeobox-containing genes GHox-7 and GHox-8 have been proposed to play fundamental roles in limb development. The expression of GHox-8, by the apical ridge cells, and GHox-7, in the subridge mesoderm, suggests the involvement of these two genes in limb outgrowth and proximo-distal pattern formation. A straightforward way to test this is to remove the apical ridge. Here we report the relationship between the mesodermal expression of GHox-7 and GHox-8 and the apical ectodermal ridge in the chick limb bud. The data from ridge removal experiments indicate that there are at least two domains of GHox-7 expression in the apical limb bud mesoderm. The posterior subridge GHox-7 domain in the progress zone requires the influence of the apical ridge for continued expression, while the anterior GHox-7 domain continues expression after ridge removal. Posterior subridge mesoderm is exquisitely sensitive to the loss of the ridge in that GHox-7 expression by these cells is reduced in only two hours and undetectable by three hours after ridge removal. It would appear that one of the ways progress zone cells respond to the apical ridge signal is by expressing GHox-7. The loss of ridge influence whether by growth at the apex or by ridge removal is followed by an unusually rapid decline in detectable GHox-7 transcripts. Maintenance of GHox-8 expression by the anterior mesoderm appears to be independent of the presence of the apical ridge.(ABSTRACT TRUNCATED AT 250 WORDS)


Hepatocyte heterogeneity in the metabolism of fatty acids: discrepancies on zonation of acetyl-CoA carboxylase. Lipid metabolism appears to be less zonated than carbohydrate and protein metabolism. Studies on the zonation of lipid metabolism have been centered in particular on fatty acid synthesis which, according to the concept of metabolic zonation, should be a predominantly perivenous process while fatty acid oxidation should be periportal. There are, however, conflicting data on the activity gradients of lipogenic enzymes as well as measurements of actual synthesis of fatty acid and very low density lipoprotein. Data obtained by microdissection show a 1.5- to 2-fold higher activity of acetyl-CoA carboxylase and citrate lyase in the perivenous zone in agreement with measurements of the actual rate of fatty acid synthesis in preparations of hepatocyte, enriched in periportal or perivenous cells. On the other hand, results obtained with the dual-digitonin-pulse perfusion technique demonstrate the opposite gradient in the form of a 2- to 3-fold higher specific activity of acetyl-CoA carboxylase in the periportal zone based on measurements of the acetyl-CoA carboxylase protein proper. This specific activity gradient, which applies to male and not female rats, disappears almost completely in the fasted-refed animal, were lipogenesis is strongly induced. In this review we attempt to rationalize these discrepancies in the results as methodological differences which in particular apply to the following parameters: (1) expression of results (reference substance); (2) selectivity of zonal sampling, and (3) differences in methodology of acetyl-CoA carboxylase measurements. It is concluded that these factors could account for the discrepancies, but further studies, in particular on the zonation acetyl-CoA carboxylase mRNA, are required in order to further understand the zonation of lipid metabolism and its possible role in the metabolic regulation of the liver.


Dopexamine hydrochloride in the human heart: receptor binding and effects on cAMP generation. Dopexamine hydrochloride is a synthetic catecholamine proposed for the short-term treatment of heart failure and postoperative low cardiac output. The pharmacological profile and anatomical localization of dopexamine binding were investigated in sections of right and left ventricle using [3H]-dopexamine and ligand techniques associated with light microscope autoradiography. Its effects on the 3-5-cyclic adenosine monophosphate (cAMP) generating system in membrane particles of the human right or left ventricle were also studied. [3H]-Dopexamine was specifically bound to sections of human right or left ventricle. The binding was time-, temperature- and concentration-dependent and was dissociable. The apparent equilibrium constant of dissociation was 3.5 nM. A decreased [3H]-dopexamine binding capacity from the base to the apex and ventricles was noticeable. The pharmacological profile of [3H]-dopexamine binding to sections of right or left ventricle was consistent with the labelling of both beta 2-adrenoceptors and dopamine DA-2 receptors. The most potent displacer of [3H]-dopexamine was the beta 2-adrenoceptor antagonist ICI 118,551 followed by dopamine, noradrenaline and domperidone. The beta 1-adrenoceptor antagonist metoprolol or the dopamine DA-1 receptor antagonist SCH 23390 were ineffective as displacers of [3H]-dopexamine binding. Light microscope autoradiography revealed the localization of [3H]-dopexamine binding sites within the wall of the human right and left ventricle. The density of silver grains was slightly higher in the right than in the left ventricle and showed a uniform transmural distribution across the ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)


Pyroglutamate aminopeptidase in rat submaxillary gland. A significant amount of pyroglutamate aminopeptidase (PGAP) activity was found to be present in 27,000 x g supernatant of rat submaxillary gland, maximum activity being at pH 6.5. EDTA stimulated the enzyme activity by 95% at pH 8.0 while at pH 6.5 it did not have any significant effect. On comparison of its properties submaxillary PGAP appears to be different from brain, pituitary and other reported PGAPs. Submaxillary PGAP could also catalyze efficiently the formation of cyclo (His-Pro) from TRH. Cyclo (His-Pro) formation by submaxillary enzyme was more pronounced than that by liver PGAP.


Generation and cytotoxic profile of human peripheral blood CD4+ T lymphocytes. The effects of a variety of metabolic and anti-tumour necrosis factor (TNF) antibodies were utilized to distinguish several different mechanisms of cytotoxicity employed by CD4+ effectors isolated from human peripheral blood lymphocytes (PBL). PBL, unseparated high buoyant density T cells and their CD4+ T cell subsets were activated with anti-CD3 monoclonal antibody (MoAb) and interleukin-2 (IL-2) for 1-5 days. CD4+ T cells activated with IL-2/anti-CD3 MoAb were cytotoxic when directed by a bispecific anti-nitrophenyl (NP)-anti-CD3 MoAb heteroconjugate against both NP-modified nucleated target cells (TC) and non-nucleated sheep red blood cells (SRBC). This CD4+ T population also lysed L929 in a TNF-alpha dependent manner. Interestingly, different mechanisms of nucleated and non-nucleated TC directed lysis by CD4+ effectors were implied by distinct patterns of sensitivity to cholera toxin (CT) and cyclosporin A (CsA). Cyclosporin A and CT inhibited CD4+ T cell directed lysis of SRBC, but not EL4. Cholera toxin, CsA or EGTA pretreatment also significantly inhibited the release of alpha-N-benzyloxycarbonyl-L-lysine-thiobenzylester (BLT)-esterase activity suggesting that degranulation of CD4+ effectors may be a critical step in their redirected lysis of SRBC. Overall, these findings suggested that activated human peripheral blood (PB) CD4+ effectors can lyse TC by at least three distinct mechanisms: (i) a CsA-sensitive directed lysis of SRBC which correlates with exocytosis and presumably occurs via membrane lesions; (ii) a CsA-insensitive directed lysis of NP-modified nucleated TC that does not appear to involve exocytosis and is metabolically distinct; and (iii) a direct TNF-dependent lysis of TNF-sensitive TC. The highly proliferative CD4+ T cell population could be propagated for at least 35 days while retaining cytotoxicity and secreting up to 80 U/mL of IL-2. These data raise the possibility that anti-CD3 MoAb plus IL-2 activated CD4+ T cells may prove effective in adoptive tumour immunotherapy.


An analysis of hypotensive effect of synthetic oxytocin in rabbit. Intravenous injection of synthetic oxytocin (Syntocinon) causes a fall of blood pressure in rabbit. The hypotensive response was potentiated after vagotomy and atropine. Beta-adrenergic and 5-HT blockers reduced the hypotensive response to oxytocin. Hypotensive response of oxytocin in rabbit involves two factors, activation of beta-adrenergic receptor and release of 5-HT.


Lasertripsy in the treatment of ureteral lithiasis. We submit our experience with laser treatment for ureteral lithiasis. We used the laser Candela MDL 2000 for the treatment of 62 lithiases (40 at the pelvic ureter, 16 at the iliac ureter and 6 at the lumbar ureter) in 58 patients. A semi-rigid Dretler or Gautier multiscope were used. Of the 62 calculi complete fragmentation was not achieved in 4 and they were ascended to the renal pelvis for subsequent ESWL. In 51% of the patients the ureteral catheter was left for 24 hours, and a double-J stent was used in two cases. 2 simple perforations of the ureter that were solved by means of a double-J stent; occasionally petechiae on the ureteral wall and two cases of rupture of the laser fibre tip that was easily removed with a forceps.


Cancer chemotherapy does not enhance MDR-associated 170 kd glycoprotein expression in normal blood mononuclear cells. The multidrug resistance (MDR) associated 170kd glycoprotein (P170) is expressed at a low level in normal and malignant cells, but in the latter it becomes frequently overexpressed after chemotherapy. This study evaluated P170 expression in normal blood mononuclear cells after and during cancer chemotherapy. P170 was detected by immunocytochemistry with two monoclonal antibodies (MRK-16 and JSB-1). P170 expression was low in all samples before, during and after chemotherapy. Cancer chemotherapy did not enhance P170 expression in normal peripheral blood mononuclear cells. The mechanisms enhancing P170 expression are likely to be more operative in tumor cells than in normal cells.


Systemic necrotizing vasculitis in nine young beagles. A systemic necrotizing vasculitis of unknown etiopathogenesis may be termed juvenile polyarteritis syndrome (JPS). The syndrome has been recognized primarily in young Beagles used for toxicologic studies. We studied 9 young Beagles with JPS. Affected dogs had fever (40 to 41.5 C), anorexia, and signs of pain in the cervical area. They had a characteristic hunched stance, and were unwilling to move. Laboratory abnormalities in all dogs included nonregenerative anemia, hypoalbuminemia, and leukocytosis characterized by a mature neutrophilia. Analysis of CSF revealed a moderate to severe neutrophilic pleocytosis and a mildly high protein concentration in most dogs. Signs of disease resolved rapidly with high doses (2.2 mg/kg of body weight, PO) of prednisone. If untreated, clinical signs and laboratory abnormalities had a remitting and relapsing course in most dogs. Findings at necropsy included necrotizing arteritis with fibrinoid necrosis, periarteritis, thrombosis, and intimal proliferation that most frequently affected small- to medium-sized vessels in the cervical spinal cord, mediastinum, and heart. An immune-mediated pathogenesis for this disease is suspected.


Use of human chorionic gonadotropin stimulation test to detect a retained testis in a cat. A 4-year-old male cat was referred because of aggressive behavior and spraying urine. When the cat was 6 months old, only 1 testis was found in the scrotum. When the cat was 1 year old, the scrotal right testis was surgically removed and the left testis was not found, either within the scrotum or within the abdomen. The cat developed male behavior and another laparotomy was performed 1 year later, at which time the left testis could not be located. The cat continued to show male behavior. On referral, the penis was well developed and had spines. Human chorionic gonadotropin (HCG), 500 IU, was administered IV. At baseline, 30, and 120 minutes after HCG administration, serum testosterone activity (ng/ml) was 0.68, 5.0, and 10.5, respectively. Laparotomy was performed with the cat under general anesthesia. The left testis was found in the facial plane lateral to the symphysis pubis. Six weeks after the surgery, the HCG stimulation test was repeated and testosterone was not detected in any serum sample. The most practical solution to locate the undescended testis would have been to follow the intact ductus deferens to the testis adjacent to the pubic symphysis.


Quantitative analysis of immunocompetent cells in human periapical lesions: correlations with clinical findings of the involved teeth. Human periapical lesions develop as a result of a pathological immune response to continuous stimuli from infected root canals. This study identified the immunocompetent cells in such lesions immunohistochemically and quantified them to examine their interrelationships and correlations with clinical findings. The number of IgG-containing cells in CD4+ cell (Th/i)-rich lesions (> or = 55 CD4+ cells/2 x 10(4) microns 2) was significantly larger than in CD4+ cell-poor lesions (< 55 CD4+ cells/2 x 10(4) microns 2). This indicated that the CD4+ cells and the IgG-containing cells acted together against antigenic stimuli. The proportion of T cells in the mononuclear infiltrates varied with the size of the periapical lesions. The proportion of CD11+ cells (monocytes/macrophages) was significantly larger in lesions which showed a positive reaction to percussion or were tender on palpation than in the lesions without these symptoms. These observations suggest that T cells may play an important role in the development of periapical lesions and that CD11+ cells may be involved in the development of symptoms.


[Urinary N-acetyl-beta-D-glucosaminidase and gamma-glutamyl-transpeptidase activities for evaluation of renal disturbance in patients with multiple myeloma]. The activities of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl-transpeptidase (gamma-GTP) and NAG isoenzyme were measured in the urine of 20 patients with multiple myeloma (IgG/IgA type/Bense Jones type; 15/1/4 cases) and 25 healthy controls to evaluate these activities as indicators of renal disturbance in multiple myeloma. NAG isoenzyme fractions in urine were measured by agarose electrophoresis-m-cresol sulfonphthaleinyl-NAG reaction. Mean urinary NAG activity in the patients with myeloma was significantly higher than that in the controls (20.1 +/- 3.3 vs 4.3 +/- 0.3U/g. cr; p < 0.001). Urinary NAG activity in these patients correlated positively with the dose (mg/g. cr) of urinary protein (r = 0.755; p < 0.01), most of which were considered to be light chain protein, but not with creatinine clearance. Each urinary NAG isoenzyme fraction (NAG-1, -2, -3) was higher in the patients than that in the controls, and especially NAG-2 fraction (A form) showed a highly positive correlation with the dose of urinary protein. Urinary gamma-GTP activity in the patients did not differ from that in the controls, but urinary NAG/gamma-GTP ratio was higher in the patients, and reversely correlated with creatinine clearance (r = -0.721; p < 0.01). It is suggested that the elevation of urinary NAG activity results from the damage of lysosome in proximal tubular cells by urinary light chain protein and its degradation products. Therefore, urinary NAG activity may be a good index for proximal tubular disturbance, and NAG/gamma-GTP ratio may be an index for the extensive damage of nephrons in addition to the damage of tubular cells in multiple myeloma.


[Indications and timing of the most frequent elective pediatric surgery interventions]. The most common surgical diseases in childhood that need a planned operation, are described--especially the indications and the timing of operation. Inguinal hernia, hydrocele, cryptorchism, umbilical hernia and phimosis are presented.


[Genetics and hyperphenylalaninemias in 1992]. Hyperphenylalaninemias result from different enzymatic impairment, the most common and best studied which is phenylalanine hydroxylase (PAH) deficiency. The PAH gene has been cloned, sequenced and mapped: it is a single copy. Twenty-one mutations have now been characterized, but they constitute less than half of the haploid genotypes in French patients. A study of RFLP haplotypes is informative in 90% of families, but no linkage disequilibrium exists between illness and one particular haplotype. Prediction of phenotype from genotype seems possible, and could constitute a better therapeutic approach, perhaps including gene therapy in the most serious cases. The recently produced murine model should permit further progress to be made. Some hypotheses could be put forward about the origin and high frequency of this disease, that principally affects Caucasians: there is a consensus of opinion--though there is no definitive proof--that some selective advantage exists in individuals heterozygous for a PKU allele.


Isolation of a new human pseudogene for proliferating cell nuclear antigen. A new gene, which cross-hybridized with a rat PCNA cDNA probe, has been isolated from a human genomic cosmid library. A comparison of the gene with the human PCNA cDNA revealed 71% homology for the nucleotide sequences. This gene completely lacks introns and has traces of a polyA tail which the messenger RNA of the active gene retains. These facts indicate that this gene was generated by the reverse-transcription of a processed RNA for PCNA and exists as a PCNA pseudogene in the human genome.


The neuroanatomical basis of anxiety.

The neuroanatomical basis of anxiety. This review details the neural systems that are important in anxiety-related behaviours. In particular, the role of the amygdaloid complex, Papez circuit, septohippocampal formation and raphe nuclei are described and discussed. Evidence is gathered from a variety of experimental approaches. These include behavioural assessment of anxiety in animals after intracerebral injection of pharmacological agents and following lesions of discrete brain nuclei and selective neurotransmitter pathways. Further evidence is provided by functional brain mapping studies applied to animals and humans. It is proposed that the neural systems recruited in different experimental conditions of anxiety may differ, supporting the notion that clinical anxiety exists in several forms. This has implications for the identification of new anxiolytic treatments. In particular, the findings suggest that approaches aimed at identifying new anxiolytic agents must take into account both the distribution of receptors for the drug and the neuronal systems activated by the experimental protocol.


Failure to replicate linkage between chromosome 5q11-q13 markers and schizophrenia in 28 families. Sherrington et al. (1988) reported linkage between markers located on the 5q11-q13 region of chromosome 5 and schizophrenia in five Icelandic and two British families. To date, however, all attempts to replicate the initial finding have failed. Using three markers of chromosome 5, we have studied 28 additional French pedigrees. When our data were analyzed both with parametric (i.e., lod scores) and nonparametric methods, we found no evidence of linkage. Thus, we were unable to replicate the earlier report by Sherrington et al.


Regulation of somatostatin and growth hormone-releasing factor by gonadal steroids in fetal rat hypothalamic cells in culture. The mechanism underlying the sexually dimorphic pattern of growth hormone (GH) secretion in the rat has not been clearly elucidated. In the present study, we assayed the possible direct effect of gonadal steroids on both somatostatin (SS) and growth hormone-releasing factor (GRF) in fetal rat hypothalamic cells in culture. Hypothalamic cells, obtained by mechanical dispersion, were maintained as monolayer cultures in serum-supplemented medium. After 20 days in culture, cells were incubated with serum free medium containing testosterone (T, 10, 20, 40 ng/dl) or estradiol (E, 0.1, 1, 10 ng/dl) for 48 h. At the end of the experiments, immunoreactive SS (IR-SS) and immunoreactive GRF (IR-GRF) were measured by specific radioimmunoassays (RIAs) in media and cell extracts. After 48 h of incubation with testosterone, somatostatin in both media and cells was significantly reduced. On the contrary, this treatment lead to a dose-dependent increase in media and cell GRF content. When cells were incubated with estradiol for 48 h, a significant inhibition in medium SS release was observed, whereas intracellular SS slightly increased at the highest concentration of 10 ng/dl. Estradiol treatment resulted in an inconsistent decrease in media and cells IR-GRF. Our results indicate that both SS and GRF are under the influence of testosterone and estradiol acting at the hypothalamic level, and furthermore suggest that at this stage of brain development, gonadal steroids may regulate GH secretion through their ability to modulate hypothalamic SS and GRF.


[Which medical treatment after myocardial infarction?]. Patients leaving the hospital after a myocardial infarction are given a prescription containing several drugs. The purpose of this paper is to determine which of these drugs have a proven value and for which types of patients. Antithrombotic agents (be it acetyl-salicylic acid or antivitamin K drugs) have been shown to be efficient after a myocardial infarction. Beta-blockers are certainly useful, notably in cases with severe necrosis. Conversely, the usefulness of calcium antagonists for secondary prevention has not been demonstrated and indeed, it seems probable that the drugs of this class might be harmful in patients who had severe infarction. There is little divergence concerning the necessity to control the risk factors for coronary atherosclerosis after a myocardial infarction. The evidence is strong concerning giving up smoking; it is intuitive as regards controlling arterial hypertension and more controversial as regards the need for lowering blood cholesterol levels. The systematic prescription of antiarrhythmic agents after myocardial is certainly noxious. Finally, prospects are now opened by the prevention of left ventricular remodelling under treatment with angiotensin-converting enzyme inhibitors.


Tolerance during dosing with H2-receptor antagonists. An overview. Diminution of antisecretory effect of H2-receptor antagonists with repeated oral dosing, termed tolerance, has been established in healthy volunteers. Anecdotal evidence indicates the development of tolerance with intravenous dosing. These findings demonstrate that tolerance may be clinically relevant in diseases where tight control of acidity is required. Patients with duodenal ulcer disease, however, do not develop significant tolerance, according to the sparse investigations available. Tolerance will, at most, only be of minor clinical significance in failures of DU to heal. The mechanisms implicated in the development of tolerance remain unclear.


On the relationship between the inhibition of thrombin stimulated aggregation and thromboxane formation in isolated platelets treated with beta-adrenoceptor blocking drugs. Thromboxane B2 (TXB2) formation in isolated, thrombin-stimulated rat platelets was time dependent and appeared after 5 s of incubation. Beta-adrenoceptor blocking (BAB) drugs inhibited thrombin-stimulated TXB2 formation in the following rank order of potency: metipranolol approximately alprenolol approximately propranolol > oxprenolol > practolol. Atenolol was ineffective in inhibiting TXB2 production in stimulated platelets. The inhibition of thrombin-stimulated TXB2 formation by BAB drugs correlated with their inhibitory effect on thrombin-stimulated platelet aggregation, arachidonic acid liberation from membrane phospholipids and with their membrane fluidization. The higher was the liposolubility of the beta-adrenoceptor blocking drugs investigated, the higher was their inhibition of stimulated TXB2 formation. Hydrophilic, selective atenolol and practolol revealed slight or no inhibitory effect on stimulated thromboxane production.


Role of CD8+ in late opportunistic infections of patients with AIDS. We studied the relationship of CD4+ and CD8+ depletion to initial and late opportunistic infections in 62 patients with AIDS. The mean interval between initial and late infections was 12.2 months. Geometric mean (and 95% confidence intervals) of T-cell counts at the diagnosis of each infection were: (Pneumocystis carinii pneumonia) CD4+ 0.051 (0.044-0.058) x 10(9)/l, CD8+ 0.561 (0.476-0.646) x 10(9)/l; (cytomegalovirus retinitis) CD4+ 0.025 (0.019-0.031) x 10(9)/l, CD8+ 0.333 (0.183-0.483) x 10(9)/l. Mycobacterium avium-intracellulare bacteraemia closely followed cytomegalovirus dissemination. Most patients were free from late opportunistic infections caused by disseminated cytomegalovirus and M. avium-intracellulare until CD8+ declined below 0.500 x 10(9)/l. Zidovudine improved CD4+, but less so CD8+, and similarly enhanced the survival of patients treated in 1985-1990 and 1991.


The use of dopexamine after cardiac surgery: acute and long-term effects in patients with impaired cardiac function. The haemodynamic efficacy of dopexamine, a beta 2-adrenergic agonist with dopaminergic activity, was evaluated during dosetitration and longterm infusion in 20 cardiosurgical patients with low cardiac output following coronary artery bypass grafting and/or valve replacement or repair. After infusion of four doses (1, 2, 4, and 6 micrograms/kg/min), the dose producing the optimal response was administered for up to 36 h. Dopexamine infusion resulted in a dose-dependent significant increase in cardiac index (CI: 2.2-->3.3 L/min/m2) associated with a marked reduction of systemic vascular resistance (SVR: 1820-->1144 dyn.sec.cm-5). Heart rate increased significantly (HR: 89-->117 beats/min), while mean arterial blood pressure remained unchanged (MAP: 94-->89 mmHg). Unwanted effects (tachycardia and hypotension) were chiefly seen at higher doses (-->4 micrograms/kg/min). The beneficial haemodynamic effects were well maintained during the extended infusion period up to 36 hours at a mean dopexamine dose of 2.8 micrograms/kg/min. At these low doses, the positive chronotropic response to the drug remained within the limits of clinical acceptability. During long-term infusion up to 36 hours there was no indication of tolerance or an effect attenuation. It can be concluded that dopexamine acting as "inodilator" with dopaminergic properties is an useful adjunct to the pharmacological spectrum in the management of low-output states following cardiac surgery.


Imaging of the testicle: the painful scrotum and nonpalpable masses. Scrotal pain is initially evaluated by color Doppler ultrasonography providing information on the presence or absence of flow within the testis and B Scan imaging providing important complementary information about lesions such as torsion of the appendix testis and testicular abscess. While radioisotope scanning provides similar information to color Doppler about testicular flow, it does not demonstrate the anatomy. Testicular imaging is extremely sensitive for "silent masses" and useful to evaluate palpable ones. Characteristic findings may be seen with simple testicular cysts and epidermoid cysts. Homogeneously hyperechoic masses have a variety of etiologies but are virtually always benign. A major limitation of a ultrasonography is the large number of nonneoplastic lesions which may mimic tumors.


[Primary and secondary prevention in hypertensive patients. An assessment of current status]. The effect of a long-term treatment with beta-receptor-antagonists after an established myocardial infarction is generally accepted. Beta-receptor-antagonists without intrinsic sympathicomimetic activity should be used, cardioselectivity is of lesser importance, except in patients with special problems (i.e. increased bronchial resistance, decreased peripheral blood flow etc.). Hydrophilic or lipophilic properties do not play any role. For primary prophylaxis in older hypertensives diuretics are the drugs of first line, in patients with high risk for heart- and blood-vessel diseases however beta-receptor-antagonists--eventually in combination with low doses of diuretics-should be chosen.


[New anti-arrhythmia agents].

[New anti-arrhythmia agents]. Use of class-I antiarrhythmic agents (encainide, flecainide or moricizine) to suppress asymptomatic ventricular premature depolarizations does not decrease, but rather increases mortality from cardiac events after myocardial infarction. These patients should not be treated with antiarrhythmic drugs until improved survival is shown in a controlled clinical trial. In other clinical conditions such as symptomatic tachyarrhythmias class-I agents should only be used if the expected benefit outweighs the risk of an adverse cardiac effect. The development of new class-I drugs does not seem promising. Esmolol is the first intravenous and ultrashort-acting beta-adrenoceptor blocker that can be used to treat supraventricular arrhythmias in the critical care setting; in addition, it displays high cardioselectivity. Specific class-III antiarrhythmic agents including sematilide and dofetilide have been shown to be effective against ventricular tachyarrythmias in preclinical studies, but their clinical value remains to be established. Torsades de pointes arrhythmia is an undesirable side-effect closely coupled to specific class-III action that may limit their future use. The known pharmacological profiles and limited controlled clinical studies make amiodarone and sotalol promising candidates for drugs that may improve survival of patients at risk for sudden cardiac death.


[Beta receptor blockers in dilated cardiomyopathy (clinical aspects)]. Results of 16 international published studies (with a total of 397 patients in NYHA-classes II-III) concerning chronic therapy with beta-adrenoceptor blockade in idiopathic dilated cardiomyopathy were analyzed. 8 studies were placebo controlled. Under beta-blockade cardiac output increased significantly by about 15% and ejection fraction by approximately 30%, apparently due to an improvement in contractility and relaxation of LV myocardium. Therapy was tolerated without complications in 93% of patients when the loading dose was 5 to 15 mg metoprolol/d (or equivalent) and a long-term dose of 100-200 mg/d metropolol (or equivalent) was reached within 4 weeks. Patients with severe heart failure (NYHA IV) had a higher risk of complications. A positive effect of beta-blockade in IDC was achieved in most cases but not earlier than after 2-3 months after initiating therapy. Despite these positive results beta-blockade in patients with IDC may not yet be recommended generally. Sufficient results of controlled trials are still lacking. Important questions with regard to the prognosis under beta-blockade, to the effects of cardioselectivity and intrinsic activity, and to the efficacy of this kind of therapy in the presence of ACE inhibitors have not been answered. Thus, major trials with controlled design are needed.


[Importance of beta 2-adrenergic receptors in heart failure]. Substantial evidence has accumulated that in the human heart both beta 1- and beta 2-adrenoceptors coexist. As a rule, the amount of beta 2-adrenoceptors is higher in the atria (about 30% of the total beta-adrenoceptor population) than in the ventricular myocardium (about 20%). Both beta 1- and beta 2-adrenoceptors couple to adenylate cyclase and mediate positive inotropic effects of isoprenaline and adrenaline on isolated, electrically driven cardiac preparations. In the atria, stimulation of both beta 1- and beta 2-adrenoceptors causes maximal increases in contractile force; in the ventricular myocardium, however, only beta 1-adrenoceptor stimulation maximally increases contractile force, whereas beta 2-adrenoceptor stimulation evokes only submaximal increases. On the other hand, noradrenaline induces its positive inotropic effect on atrial and ventricular preparations solely via beta 1-adrenoceptor stimulation. Because nordadrenaline is the main transmitter of the human sympathetic nervous system, this indicates that under normal physiological conditions, the heart rate and contractility are under the control of cardiac beta 1-adrenoceptors, whereas cardiac beta 2-adrenoceptors play only a minor role, if at all. However, in situations of stress, when large amounts of adrenaline (acting at both beta 1- and beta 2-adrenoceptors with the same affinity) are released from the adrenal medulla, activation of cardiac beta 2-adrenoceptors may contribute to an additional increase in heart rate and/or contractility. In chronic heart failure, cardiac beta-adrenoceptor function decreases (presumably due to endogenous "downregulation" by the elevated catecholamines) and this decrease is related to the severity of the disease (judged clinically by NYHA functional class).(ABSTRACT TRUNCATED AT 250 WORDS)


Mapping quantitative trait loci for behavioral traits in the mouse. After many years of studying various behavioral characters in the mouse, it is clear that most are heritable and are specified by complexes of genes or quantitative trait loci (QTLs). In order to attain a more complete understanding of the genetic causes of individual differences in behavior, the mechanism of action of these QTLs must be elucidated. The most straightforward approach to determining the mechanism of action of a particular QTL is to identify and molecularly clone the gene; this can be done by positional cloning, which depends on precise knowledge of the genetic map position. As the genetic data base for the mouse genome continues to develop, such strategies will become increasingly easy to perform. Here we suggest a multistage strategy for QTL mapping using recombinant-inbred strains of mice: (1) characterize genomic DNA from parental strains originally used to generate the RI strains; (2) characterize the RI strains for a quantitative character and for DNA markers that differ in the parental strains; and (3) assess the quantitative character in F2 mice derived from crosses between the parental strains, then determine the genotypes of extreme F2 mice for markers that account for at least 5% of the additive genetic variance. Data from these F2 crosses can be used to test hypotheses from the analysis of RI strains, i.e., that a QTL maps to a particular region. Using data from the mouse genome data base, this strategy should allow the molecular identification of the gene based on a candidate-gene approach. We illustrate the approach with examples from our work in mapping QTLs specifying neural sensitivity to the anesthetic effects of ethanol.


Immunoreactivity of an antibody to a beta/A4 sequence with Alzheimer paired helical filaments and tau protein. beta/A4, a peptide that forms the extracellular amyloid fibrils of Alzheimer senile plaques, has also been proposed to be a component of Alzheimer paired helical filaments (PHFs). We compared BR88, an antiserum to amino acids 1-12 of beta/A4, with BR126, an antiserum to the sequence SEKLDFKDRVQS in tau protein, since tau protein is the only confirmed component of PHFs. In enzyme-linked immunosorbent assays (ELISAs), both antibodies reacted with pronase-treated PHFs better after PHFs were treated with guanidine. tau protein shares no sequence homology with beta/A4. Nevertheless, BR88 cross-reacted with human recombinant tau isoforms by ELISA and Western blot analysis with potencies comparable to those for anti-tau antibodies. BR88 reacted with a beta/A4 peptide as well on a molar basis as with tau protein and showed some reactivity to the tubulin-binding region of tau protein. In conclusion, the beta/A4 antiserum BR88 cross-reacts with tau protein, possibly explaining its reactivity with PHFs.


Beta-blockers, calcium channel blockers and the sulfhydryl-ACE inhibitors demonstrate protection against free-radical-mediated injury of cardiovascular cells and membranes. During reperfusion of previously ischemic cardiac tissue, oxygen-centered free radicals are generated and may result in peroxidative injury of cardiovascular cells and membranes. Since the occurrence of reperfusion injury in patients is unpredictable, particularly in those patients with chronic ischemic coronary artery disease, silent ischemia and those predisposed to significant coronary spasm, it would be advantageous to provide continuing therapy with antioxidant agents.


Establishment of cytotoxic CD4+ T cell clones from cancer patients treated by local immunotherapy. We have previously reported that the antitumor effect of OK-432, a Streptococcal preparation, is markedly augmented when injected intratumorally together with fibrinogen (Cancer, 69: 636-642, 1992). In order to elucidate the mechanism of the antitumor effects, we established T cell clones from regional lymph nodes of colorectal cancer patients who received this local immunotherapy. By culture of lymph node lymphocytes, in the presence of IL-2 and OK-432, 4 clones of T cells were established from 4 patients treated by local immunotherapy. These clones had a helper T cell phenotype (CD3+, CD4+, CD8-, CD56-, WT31+) and were successfully maintained for several months. The cells strongly expressed CD25 when stimulated with OK-432 and exhibited a high level of cytotoxic activity in part explained by the increased expression of ICAM-1 and LFA-1, and the release of TNF beta. These results suggest that the CD4+ T cells play a role in the antitumor mechanism of local immunotherapy.


[The effect of adrenoblockers on the neurons of the lateral hypothalamus under the action of pentagastrin]. To test the hypothesis of interaction pentagastrin (PG) noradrenaline (NA) in central neurochemical mechanisms of food motivation, we studied the activity of single neurons in lateral hypothalamus (LH) after s.c. PG injection. Following PG injection microiontophoresis (MIF) of propranolol prazosin was made. PG-induced changes were similar to neuronal activity in rabbits LH after 24-hour food deprivation in 59%. Propranolol-induced changes were following firing pattern in the process of food uptake in 68%. Prazosin MIF induced firing pattern of neuronal activity of saturated rabbits in 60%.


[Stress-inducing behavioral changes and the functions of the neurohormonal systems in monkeys of different social ranks]. As a result of intensive stressful stimuli hamadryas baboons developed, depending on their hierarchic status, depression-like states varying in severity. Their development correlated with a drastic release of biogenic amines, activation of pituitary-adrenal system and inhibition of hormonal function of the gonads. It is shown that dominant and low-rank monkeys, in spite of the differences in their initial psychoemotional states and in the blood levels of mediators and hormones, demonstrated marked disintegration in their individual and social behavior. There was a larger increase in the blood concentrations of dopamine, serotonin and cortisol and more significant inhibition of testosterone production under the influence of two-hour immobilization as compared to the subdominant animals.


[An analysis of the ionic regulation of the specific binding of 3H-diazepam depending on the phenotype of the emotional stress reaction]. It was shown that low NaCl concentrations (less than 50 mM) had more pronounced stimulatory effect on [3H]-diazepam ([3H]-DZ) binding in brain membranes of Balb/c (C) mice than in C57B1/6 (B6) mice. These interstrain differences disappeared after emotional stress in "open field" (OF) test. Low doses of diazepam (0.75 mg/kg) and hydazepam (1 mg/kg) induced anxiolytic effect in C mice and restored their normal [3H]-DZ binding level in the presence of NaCl. On the opposite, effects of the same doses of the benzodiazepines were not revealed either on the behavior in OF test or on stimulating properties of NaCl in B6 mice. Both benzodiazepines (10 mg/kg) induced similar behavior (sedative) and receptor (decrease of NaCl stimulating ability) in B6 and C mice. We made a conclusion that the ability of NaCl to increase [3H]-DZ binding is a physiological index which reflects hereditary differences in emotional-stress reactions and behavioral effects of benzodiazepine tranquillizers.


[The potential-dependent action of the opioid peptide dermorphin]. Dermorphin action was studied on cross-section strip of frog stomach muscle by a mechanographic recorder. The results show that dermorphin (10(-5)-10(-8) M) blocks acetylcholine effects, spontaneous activity and muscle contractions induced by direct electrical stimulation. All the above effects are hardly reversible. Dermorphin fails to block spontaneous and evoked activities if it is injected into the incubated medium during K(+)-depolarization (KCI--100 mM) of the muscle. Thus, dermorphin has voltage-dependent action. The discussion deals with dermorphin action on voltage-dependent Ca(2+)-channels of muscle cell membrane.


Takayasu's aortitis with renovascular hypertension. We report a case of Takayasu's disease with severe renovascular hypertension in a girl from Eritrea. In the "burn-out" phase after the erythrocyte sedimentation rate had normalized, reconstructive vascular surgery was performed as further progression of the disease seemed unlikely. However, probably due to her growth, the graft rotated and a second operation was successfully performed.


Management of dental injuries.

Management of dental injuries. Dental-related injuries, which range from chipped teeth to fractured jaws, are among the most common injuries seen in schools. This article describes the various injuries and provides guidelines, for the nurse's actions at the scene, to ensure the greatest potential for successful treatment. Guidelines are also given for informing other school and associated health personnel about dental emergencies.


PC-10 antibody to proliferating cell nuclear antigen (PCNA) is not related to prognosis in human breast carcinoma. The PC-10 monoclonal antibody to PCNA was employed to analyze proliferative grade in conventionally-formalin fixed, paraffin-embedded tumour samples of 162 patients with primary breast carcinoma. To perform the immunocytochemical method, sections were not heated, were de-waxed using alcohol, and then immersed in a phosphate-buffered saline solution and in methanol with 0.5% hydrogen peroxide to block endogenous peroxidase activity. Immunostaining was performed by a streptavidin-biotin peroxidase substrate. A semiquantitative scoring system was used to evaluate the fraction of nuclei that were PCNA-positive. The score ranged from 0% to 75% with a median value of 25%, mean of 27.8 +/- 1.5. PCNA staining was significantly associated with oestrogen receptor-negativity (p = 0.011) and correlated, but not at a statistically significant level, with tumour size (p = 0.08). No significant association was observed between PCNA and node status, grading, DNA ploidy, progesterone receptor or menopausal status. Prognostic indices such as number of positive lymph nodes and DNA ploidy were significantly associated with relapse-free survival (RFS) and overall survival (OS). No significant correlation between PCNA nuclear immunostaining and RFS or OS was observed after a median follow-up of 4 years. Our results indicate that analysis of PCNA alone does not seem to be a useful marker in identifying patients at different prognosis in human breast cancer.


Multidrug resistance (MDR) gene expression in acute non lymphoblastic leukemia: sequential analysis. Sequential evaluation of P-glycoprotein expression was performed in 29 patients with acute nonlymphoblastic leukemia using immunocytochemistry with the C219 antibody. At diagnosis, 32% of the patients exhibited more than 5% of the P-gp(+) leukemic cells. Under chemotherapy, 62% of the patients eventually expressed a subset of P-gp positive leukemic cells. After conventional doses of cytosine-arabinoside (Ara-C) and daunorubicin or mitoxantrone, positive P-gp cells were noted in 65% of the cases. This percentage was significantly higher (p = 0.002) than the proportion of positive cases (15%) observed after regimens containing either intermediate doses of Ara-C or cyclosporine A, a P-gp modulator.