[Programs of mass and selective screening of pregnant women in prenatal studies. Screening of alpha fetoprotein in the blood serum of the mother]. The total of 38479 echography studies and 25147 alpha-fetoprotein estimations in mother blood serum have been performed upon prenatal screening. 445 congenital developmental defects are revealed. AFP base and limiting values (2.5 MoM and 0.5 MoM) are found. AFP values and echocardiography results in the nor and in genetic syndromes of multiple congenital developmental defects are compared. It is found that AFP values are higher than MoM or only slightly higher than Me in the same syndromes. The different level of AFP for the same syndromes appeared to be associated with the phenomenon of overlapping due to the clinical polymorphism and type of injury of the nervous system and with the extent of changes in placenta, amniotic fluid and umbilical cord were revealed in 99% of syndromes. The increased AFP level can be considered as a marker to detect signs of the genetic syndromes. Low AFP level peculiar to aneuploidy appeared to be normal or increased. The AFP test can be used as a marker of changed embryogenesis.


[Possibilities and prospects of the use of DNA analysis in the diagnosis and prevention of inherited disease in the Ukraine]. The results from molecular genetic analysis of some mutations in the 10th and 11th exons of cystic fibrosis transmembrane regulator (CFTR) gene as well as of deletions in the 8, 17, 19, 43, 50, 60th exons of dystrophin gene in 61 CF-families and 21 DMD-families from different Ukraine regions are presented. It was shown that delta F508 frequency of CF-patients was 59.2%, the frequencies of S5491, G551D and K533X were about 1%. The frequency of delta F508-carriers analysed among 365 healthy donors from different regions of Ukraine was 1:40. The analyzed deletions of dystrophin gene were revealed only among 6 DMD-patients. The associations of analyzed mutations of CFTR gene and DMD-gene with RELP's in 4 loci of chromosome 7 and 2 loci of X-chromosome, respectively, were found. The results of prenatal diagnosis of cystic fibrosis and DMD are presented.


In vitro investigations on cellular damage induced by high energy shock waves. Single-cell suspensions of the prostate carcinoma cell line PCA were exposed to electromagnetically generated ultrasound shock waves (source and focusing lens identical to those used in the commercially available lithotripor Lithostar Plus). Cell loss of up to 40% occurred in sample tubes containing air. To expose multicellular tumor spheroids and cells growing on a microcarrier, an experimental setup was developed that prevented motion of the specimen. Intracellular damage of intact spheroids was analyzed by laser scanning microscopy following specific fluorescence staining. Different sensitivities of individual cell components with respect to the applied energy density of the pulses were found, namely defects on cell membranes (0.12 mJ/mm2), vimentin (0.21 mJ/mm2), mitochondria (0.33 mJ/mm2) and nuclear membranes (0.5 mJ/mm2). Loss of cells growing on a microcarrier was found after application of 200 pulses with 0.21 mJ/mm2.


Immunogold localization of actin and cytokeratin filaments in myoepithelium of human parotid salivary gland. Myoepithelial cells of salivary gland are uniquely specialized cells; their function is unclear, but the considerable complement of muscle-specific actin suggests contractility is one function. By routine transmission electron microscopy myofilament visualization is variable. Some myoepithelial cells appear to have limited and only focal aggregates of myofilaments, while others seem to have readily appreciated myofilaments within a longitudinally oriented cytoplasmic zone at the basal portion of the cell. However, immunogold electron microscopy using the anti-muscle-specific actin antibody, HHF35, while indicating a basal distribution for the muscle-isoform of actin in a platelike fashion in certain myoepithelial cells, also reveals that others associated with both intercalated ducts and acini have a more generalized distribution of myofilaments throughout the cytoplasm. Actin was also noted within tonofilaments and double immunogold labeling using both the HHF35 and AE1/AE3 (anticytokeratins) antibodies confirmed the variable interrelationship of these two filaments. Within any one myoepithelial cell, actin and cytokeratins might colocalize in some areas of the cytoplasm containing filaments, but not in adjacent zones. These results suggest that intermediate filaments and myofilaments are complexly organized in myoepithelial cells, and that quantitative and qualitative differences exist in the expression and distribution of intermediate filaments and myofilaments. These cells are likely structurally, if not functionally, heterogeneous.


[Technical recommendation for connecting osteosynthesis]. In patients with pathological fractures an operative stabilisation is indicated without delay although 40 to 50% of the patients survive only three to four months. Generally palliative operations are practiced. Mostly a connecting osteosynthesis is carried out in which after resection of the tumorous bone the stability can be achieved by the application of plates and filling of the bone defect with cement. In three examplary cases a technical improvement of the impaction of bone cement is described. Using an exactly cutted packing ring of a single use syringe after the application of the plate the bone cement can be filled in easily. By the casting a penetration of the bone cement into the soft tissues can be avoided. An additional effect is that pins of cement extend into the bone narrow with a sufficient support of the filling on the cortical bone. After the removal of the casting the screws can be inserted in the overbridged defect while the polymerisation has nearly finished.


Use of combined myeloperoxidase and immunogold technique in hybrid leukemia: a case report. A case of hybrid leukemia is presented. A 30-year-old man had two blast cell populations with bone marrow. The majority of the blast cells had B-lymphoid markers on their surfaces and a small number of cells had both lymphoid markers and penoxidase activity on the same cell. Immunoelectron microscopy combined with ultrastructural cytochemistry (MPO reaction) demonstrated the biphenotypic nature of the blast cells.


Radical cystectomy in regionally advanced bladder cancer. The distinction pathologically of invasive tumors confined to the muscularis propria from those that penetrate the bladder wall and invade the perivesical fat or adjacent organs is a critical prognostic determinant. Nodal metastases are evident in approximately one half of patients with tumors pathologically staged as P3b or greater. Five-year survival rates after radical cystectomy with or without preoperative irradiation for stage P3b tumors range from 17% to 46%. Long-term survival is the exception when bladder cancer invades the pelvic sidewall or adjacent structures, yet cystectomy can provide palliation and accurate staging and can be considered in the context of combination therapy. Supravesical diversion can provide palliation when there is nodal disease above the bifurcation or pelvic fixation. The optimal role of adjuvant chemotherapy in the treatment of regionally advanced bladder cancer is yet to be defined. Tannock has delineated the many serious pitfalls inherent in interpreting nonrandomized trials of new therapies (see also his article elsewhere in this issue). Randomized trials are currently under way to determine if survival can be improved with adjuvant or neoadjuvant chemotherapy and the most efficacious timing of chemotherapy administration. Clinicians should generally resist the tendency to treat all patients with these regimens until it is clear that we are truly improving the outcome of therapy and the quality of life for our patients.


Metastatic bladder cancer. Natural history, clinical course, and consideration for treatment. Patients with metastatic transitional-cell carcinoma of the bladder have a poor prognosis with brief survival. Controversy exists as to the clonality of bladder cancer, as well as the natural history of muscle-invasive disease that subsequently becomes metastatic. Newer molecular biologic techniques may help us identify and understand the molecular changes involved in transforming normal urothelium into the malignant phenotype. In addition, newer chromosomal markers may enable us to determine the prognosis and the potential for progression to invasion and metastases. Additional work to find the optimum doses and dosing schedules and combinations of chemotherapeutic agents for metastatic transitional-cell carcinoma will be necessary before we can improve survival for all patients with this disease.


Is open prostatectomy really obsolete?

Is open prostatectomy really obsolete? A total of 1,066 prostatectomies treated by us from 1985 to 1989 were reviewed. The necessary comprehensive data were available on 710 cases. Open (Millin's retropubic) prostatectomy (RPP) was the procedure of choice for large glands and transurethral resection (TURP) for smaller glands: 408 had had RPP and 262 TURP; 14.5 percent of the TURP group eventually needed a second procedure during a one to six-year follow-up compared with only 2.6 percent of the RPP group. Forty other patients who had been operated on elsewhere were referred to us for a second, repeat procedure; 30 also previously had had a TURP. Total hospitalization, operating time, and complications were better in the long run in the RPP group compared with the TURP group. It is believed that open prostatectomy still has a respectable place in urology and therefore, should be considered and also taught to residents for use in dealing with large glands.


Malignant schwannoma of kidney capsule.

Malignant schwannoma of kidney capsule. This report is of a malignant schwannoma originating in the capsule of the right kidney. Using sonography, nephroangiography, cavography, computer tomography, and bone scanning, metastases in the kidney or a retroperitoneal tumor could be diagnosed. After transperitoneal exploration, the right kidney and mesenteric metastases were removed. Due to tumor infiltration into the liver and tumor masses in the retroperitoneum, only nephrectomy and palliative excision of retroperitoneal metastases were done. Pulmonary metastases developed postoperatively, and the patient died three months after the operation.


[Antiviral strategies in the replication of human immunodeficiency virus]. The replication cycle of any virus involves a number of steps, beginning with specific attachment to a cell surface receptor leading eventually to production of progeny viruses by infected cells. In the case of the immunodeficiency virus type-1 (HIV-1), the first step involves a specific interaction between the gp120 viral envelope surface protein and specific CD4 receptor sites at the cell surface. This is followed by penetration of the virus into cells and the formation of proviral double-stranded DNA from single-stranded viral RNA, a process mediated through the action of the viral enzyme called reverse transcriptase. This, in turn, leads to the migration of proviral DNA into the nucleus of the cell and the integration of such DNA within the host cell genome. Finally both viral RNA and viral proteins are produced by the cell's genetic apparatus and new viruses are assembled at the cell surface. The fact that integration of viral DNA into host cell chromosomes occurs means that any cellular replication event will be accompanied by replication of viral DNA. Each of these steps represents a potential target for anti-viral chemotherapy. To date, most efforts to treat HIV-associated disease have focused on the reverse transcription step. In this respect, zidovudine (AZT) has been the most widely used anti-viral drug studied. However, the relative toxicity and lack of efficiency of this drug means that our efforts to develop new therapeutic strategies to combat HIV infection must continue.(ABSTRACT TRUNCATED AT 250 WORDS)


An outbreak of melioidosis in imported primates in Britain. An outbreak of melioidosis, a bacterial infection caused by Pseudomonas pseudomallei, was identified in a batch of feral cynomolgus monkeys (Macaca fascicularis) imported to Britain from the Philippines. Thirteen confirmed or possible cases occurred among a batch of 50 animals. Subsequent investigations revealed that the infection was uncommon among imported primates from a variety of sources, although three other cases were identified in monkeys imported from Indonesia. The majority of the affected monkeys had splenic abscesses, and hepatic abscesses and infections of the soft tissues and skin were also frequently observed. Most of the infected animals had no clinical signs despite extensive abscesses, and the presence of infection was only suspected when they were shown to have serum antibodies to P pseudomallei by an enzyme-linked immunosorbent assay. Although there was no evidence of cross infection of other animals or human handlers, this outbreak is a reminder of the dangers of working with wild-caught primates and the potential for the establishment of environmental foci of melioidosis.


Feline spongiform encephalopathy: fibril and PrP studies. The brains from 18 cats were examined for the presence of the fibrils and modified PrP protein which are molecular diagnostic markers for scrapie-like diseases. Thirteen cats were referred with clinical neurological signs potentially indicative of feline spongiform encephalopathy (FSE). Of these, five had histopathological changes of FSE, five had other lesions of the central nervous system, and in three the brain was normal. The remaining five cats had no clinical neurological signs and were selected as controls. Fibrils and modified PrP protein were found in the brains of the five cats with FSE and in one of the cats with neurological signs but no histopathological changes in the central nervous system. Fibrils were present in the absence of modified PrP in the brains of two cats, one with neurological signs and a histologically confirmed meningioma, and one with no neurological signs and a histologically normal brain.


Equine hyperlipaemia in the United Kingdom: clinical features and blood biochemistry of 18 cases. The background, clinical signs, blood biochemistry and management of 18 cases of equine hyperlipaemia are described. Eleven of the animals were Shetland ponies, four were Welsh mountain ponies or their crosses, one was a fell pony and two were riding ponies of mixed breeding. Their average age was nine years. Fourteen of the cases were mares, of which nine were in foal and two were lactating; the remainder were geldings. Underlying or concurrent diseases were identified in only six animals, but in one other animal the hyperlipaemia appeared to have been precipitated by stress, and in another by undernutrition to prevent laminitis. Twelve of the animals were considered obese. There was no age, seasonal, or geographic bias to the distribution of cases. Plasma triglyceride concentrations were increased by between five- and 80-fold, and ranged from 4.7 to 78.8 mmol/litre. There was biochemical evidence of hepatic damage in 17 cases, of renal insufficiency in 15, and pancreatic pathology in three cases. Four animals were euthanased without therapy. The others were treated with oral glucose solutions, which were supplemented with injections of insulin and heparin in four cases, and insulin alone in two cases. Eight of the treated animals died, to give an overall mortality of 67 per cent. The outcome of the treatment was unrelated to the degree of hypertriglyceridaemia, to the presence and severity of hepatic, renal or pancreatic pathology or to the therapeutic regimen.


Early immunodiagnosis of bovine fascioliasis using the specific antigen f2 in a passive hemagglutination test. An improved hemagglutination (HA) test using the purified specific f2 antigen of Fasciola hepatica has been evaluated with regard to its potential use for early diagnosis of infection. On experimental infection of beef calves 6-8 months of age, f2-specific antibodies were detected 2-4 weeks after inoculation and persisted at high levels during the 28 week experimental period. On natural infection of dairy calves, 6-9 months of age, allowed to graze in infected fields from April to June, 48% of the animals were positive in July although coproscopic analyses were negative. In November all the calves were HA positive but only 24% of them excreted F. hepatica eggs. Beef calves 1-3 months of age allowed to graze with their dams in infected fields continued to suckle their dams and were weakly infected according to HA results. This weak infection was not detected by coproscopical analysis. Colostral f2-specific antibodies persisted for approximately 6 months in the serum of dairy calves allowed to suckle their dams immediately after birth.


Isolation and sequence of sheep immunoglobulin E heavy-chain complementary DNA. A complementary DNA (cDNA) corresponding to sheep immunoglobulin E heavy (IgE H) chain messenger RNA (mRNA) was isolated and sequenced. A fragment of sheep IgE constant H (epsilon)-chain was initially synthesized using the polymerase chain reaction (PCR) and single-stranded cDNA prepared from the mRNA of parasite-stimulated sheep lymph nodes. This fragment was then used to probe a cDNA library, again prepared from a parasite-stimulated lymph node. A recombinant clone containing cDNA encoding a sheep IgE H-chain of 1802 base pairs was isolated and the H-chain cDNA-sequenced. The nucleotide sequence was found to code for a complete sheep IgE H-chain, consisting of both variable (V) and constant (C) regions. When the amino acid sequence derived from the nucleotide sequence was compared to other species epsilon-chains, interesting homologies and differences between corresponding domains were found, including conservation in cysteine and tryptophan residues and variable glycosylation sites.


The role of insulin-like growth factors and IGF-binding proteins in the physiological and pathological processes of the kidney. Insulin-like growth factors (IGFs) and their binding proteins are implicated in the growth regulation of the kidney during embryogenesis and differentiation. Recent evidence also suggests that IGFs play a role in kidney physiology (glomerular filtration rate, renal plasma flow) and pathology (diabetic renal hypertrophy, nephritis, glomerulosclerosis, kidney tumours, chronic renal failure). This review focuses on the biology of IGFs at the molecular, protein and receptor levels and considers their importance in renal physiology and pathology. The current data demonstrate a central role for the IGFs in the mediation of a wide variety of effects on renal growth, function and malignancy.


Immunobiochemical characterization of the antigen detected by monoclonal antibody IND.64. Evidence that IND.64 reacts with the cell proliferation associated nuclear antigen previously defined by Ki-67. The immunohistochemical characteristics of the monoclonal antibody IND.64 are very similar to those of the monoclonal antibody Ki-67. The aim of this study was to further characterize this new antibody and to compare it with Ki-67 using immunobiochemical methods. Our results demonstrate that the similarity between the antibodies holds true even at the molecular level. Immunoblot analysis of IM-9-cell lysates with both antibodies showed a double band with apparent molecular weights of 395 kD and 345 kD, respectively. Competition ELISAs using a synthetic peptide derived from the thus far determined Ki-67 cDNA sequence as competitor, indicate that IND.64 may recognize the same epitope as Ki-67. The IND.64 epitope resides at least within a 20 amino acid sequence which also contains the Ki-67 epitope. Since IND.64 is of the IgG2b subclass, while Ki-67 is of the IgG1 subclass, the two antibodies may be useful for double immunostaining. In addition, IND.64 may help in determining the still unknown function of the antigen it recognizes.


Atypical micromegakaryocytes, promegakaryoblasts and megakaryoblasts: a critical evaluation by immunohistochemistry, cytochemistry and morphometry of bone marrow trephines in chronic myeloid leukemia and myelodysplastic syndromes. A morphometric analysis of bone marrow trephine biopsies has been performed to study the frequency and planimetric characteristics of so-called atypical micromegakaryocytes in chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS). In addition, an attempt was made to discriminate this particular cell population from small immature elements of megakaryocytopoiesis, such as promegakaryoblasts and megakaryoblasts. The staining reactions employed included periodic acid-Schiff (PAS), alpha-naphthyl acetate esterase (ANAE) and immunohistochemistry with a monoclonal antibody against platelet glycoprotein IIIa (Y2/51-CD61). Comparison of the various staining reactions applied to the different megakaryocytic elements together with morphometric measurements resulted in a clearcut identification of promegakaryoblasts. These were defined as the earliest immature and exclusively CD61-positive precursors. Atypical micromegakaryocytes were characterized by their dysplastic features and strong ANAE reactivity in addition to their positive CD61 staining. When stringent diagnostic criteria (diameter ranging between 10 to 15 microns, mean size about 12 microns) were applied, this abnormal cell population comprised less than 10% of total megakaryocytopoiesis in CML and MDS. It may be assumed that dysmegakaryocytic features in the latter disorders are partially generated by small to medium-sized megakaryocytes (diameter less than 30 microns). In conclusion, the relative frequency of promegakaryoblasts in the normal bone marrow (range 6-8%) is confirmed by evaluation of the immunohistochemical and cytochemical staining methods (CD61 and ANAE). Furthermore, the ANAE reaction facilitates the recognition of atypical micromegakaryocytes as well as small megakaryocytes. Thus cytochemistry provides a better insight into alterations of these cell lineages in various pathological conditions.


Farber bodies found in murine phagocytes after injection of ceramides and related sphingolipids. Mice were injected subcutaneously with a single dose of sphingolipids. The sphingolipids tested were: ceramide with alpha-hydroxy fatty acids, ceramide with non-hydroxy fatty acids, glucocerebroside, sphingomyelin, and galactocerebroside. Lipids without sphingolipids served as a control. The mice were sacrificed 1, 2, 3, 4, 5 and 7 days after injection. Three mice were used for each experiment. The subcutaneous tissue at the injected area, the liver and the spleen were studied histologically. At 1-3 days after injection, numerous cytoplasmic inclusion bodies were observed in the macrophages and fibroblasts in the subcutaneous tissue, but not in the liver or the spleen. Ultrastructural studies of the inclusion bodies indicated that the sphingolipids taken up by the phagocytes retained their respective original shape during the 1-3 day stage. At days 4 and 5, the number of the inclusion bodies decreased, but they contained Farber bodies, i.e. curvilinear bodies 12 to 25 nm wide and up to 120 nm long. The mice with galactocerebroside were an exception, with parallel leaflets structures, but without the Farber bodies.


Detection of multiple hormones and their mRNAs in human neuroblastoma cell line NB-1 using in situ hybridization, immunocytochemistry and radioimmunoassay. The production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells.


Characteristics of small cell colonies developing in primary cultures of adult rat hepatocytes. Phenotypes of the cells developing into small colonies after days of primary culture of adult rat hepatocytes in serum-free modified Dulbecco Modified Eagles' medium containing 10 mM nicotinamide and 10 ng/ml epidermal growth factor were analyzed immunocytochemically, cytochemically and ultrastructurally. Albumin, cytokeratin 8 and 18 were seen by immunocytochemical techniques in the cells of the small colonies at Day 6. Transferrin, alpha 1-antitrypsin, ceruloplasmin, and haptoglobin, proteins secreted by mature hepatocytes, were faintly stained in these cells as was alpha-fetoprotein. These proteins were secreted into the culture medium as evidenced by immunoblot analysis. gamma-Glutamyltransferase, alkaline phosphatase and glucose 6-phosphatase were not present in the cells of the small colonies as well as the surrounding hepatocytes at Day 6 of culture. In addition, ultrastructural examinations of the cells in the small colonies indicated that these cells not only had many characteristic mitochondria and desmosomes, but also a few small peroxisomes. Such cells, even after 20 days in culture were proliferating, as evidenced by the intranuclear presence of the proliferating cell nuclear antigen. The potential relation of these cells to hepatocytes which may serve as the principal reserve for replicating hepatocytes is discussed.


[Urinary amylase activity and debit as indices of the functional status of the pancreas and gallbladder]. The functional state was studied of the pancreas and gallbladder by calculation of the activity and yield of uroamylase in 96 persons. Data are compared that were obtained on the basis of this method. There was a clear correlation with results obtained during cholecystography. This simple and precise method may be recommended for wide practical use.


[Character of changes in protease inhibitory capacity of blood in experimental osteoarticular tuberculosis]. All the steps of osteoarticular tuberculosis evolution were accompanied by an increase in proteolytic activity in rabbit blood serum, which was compensated by activation of alpha 1-inhibitor of proteinases at the initial steps of osteitis. The system "proteinases-inhibitors" was imbalanced during the severe phases of arthritis independently on the rate of its development as follows: predominance of proteolytic potential over inhibitory activity, dissimilar activity of alpha 1-inhibitor of proteinases simultaneously with equal rate of alpha 2-macroglobulin content decrease. Dissimilar alterations in the system studied enabled to suggest that differential application of proteinases is suitable for treatment of inflammation with respect to the step of osteoarticular tuberculosis development.


[Ebola virus reproduction in cell cultures]. Ebola-Zaire virus production in Vero and BGM cells was studied. The CPE developed in both cell cultures. The cell monolayer destruction by 80-90% was seen at a low multiplicity of infection in 7-8 days after virus inoculation. An overlay composition was developed for virus titration using plaque assay. The plaque production was shown to be directly proportional to the virus dose. The curve of Ebola virus production in Vero cell culture fluid was determined. At a multiplicity of infection of 0.01 PFU/cell, the maximum virus titer of 10(6.4) PFU/ml was reached in 7 days postinfection. Specific antisera were generated by inoculation of guinea pigs. Indirect immunofluorescent assay was used for testing of virus-specific antigen and antibody.


[The antigenic interrelationships between influenza A (H2) viruses determined by the mathematical processing of the data from immunoenzyme analysis using monoclonal antibodies to the M1 and NP proteins]. Antigenic relationships among 15 influenza A (H2) virus strains of human and avian origin were determined by ELISA titers with monoclonal antibodies (MCA) to Ml and NP proteins. Minor antigenic variations were found in Ml protein. One MCA to NP protein (469/6) showed different reactivity with human and avian influenza viruses. Analyses of antigenic relationships among influenza viruses were performed according to a computerized taxonomic cluster procedure. The evolutionary relatedness of these viruses is discussed.


Molecular mimicry--hypothesis or reality? A number of observations support molecular mimicry as a possible pathogenetic mechanism in diseases such as acute rheumatic fever, reactive arthritis after enteric infection or associated with Reiter's syndrome, myasthenia gravis, or even in rheumatoid arthritis. Molecular mimicry can be defined as a sharing of epitopes in linear or 3-dimensional presentation on disparate proteins from entirely different sources--for instance, group A streptococcal membranes and human cardiac myosin. How exposure to or infection with organisms sharing molecular similarity with antigens of the human host can evade tolerance and actually induce a self-reacting humoral or cellular immune response is still not clear; however, a large body of evidence has now been accumulated that documents apparent molecular mimicry mechanisms in these disorders. In some diseases, the molecular mimicry appears to involve human target organs and specific components of the infectious organism, whereas in others the host HLA cell surface molecules appear to share antigens with presumed bacterial or viral initiators of disease.


[Evolution of morphological and clinical changes in mesangial proliferative glomerulonephritis]. The clinical and morphological analysis is reported of the changes evolving in 12 cases of mesangial proliferative glomerulonephritis based on repeated biopsies carried out at intervals from 1 to 7 years. Clinical findings at the time of the first biopsy included in 2 cases nephrotic syndrome, and in the remaining cases proteinuria ranging from 0.3 to 2/1000. In all cases erythrocytes in urine were present ranging from 4-6 to 50-100 erythrocytes per field of vision. Hypertension was found in 4 cases, and increased serum creatinine level in 1 patient. At the time of repeated biopsy in 11 cases clinical evidence of improvement was noted with decreased proteinuria anderythrocytes in urine. In 1 case worsening was found and several months later signs of renal failure developed which led to death. The morphological examinations demonstrated in the first biopsies mesangial proliferative glomerulonephritis. In second biopsies these findings were confirmed. In 1 case with unfavourable outcome the changes became more pronounced, and in the remaining ones no significant differences were noted in relation to the first biopsy which evidenced lack of a close correlation between the clinical condition and the morphological state of the kidneys.


[Inhibition of the reproduction of the influenza B virus by aprotinin]. Injection of aprotinin, a natural inhibitor of proteinases, into the allantoic cavity of chick embryos infected with influenza B/Lee/40 or B/HK/73 virus resulted in inhibition of proteolytic cleavage of virus hemagglutinin HA into HA1 and HA2, thereby decreasing the level of proteolytic activation of the synthesized virus particles. As a result of this inhibition in aprotinin-treated embryos, multicycle virus reproduction was limited and virus yields decreased considerably. The experimental results indicate the potential of chemotherapeutic inhibition of infection caused by influenza B viruses using antiproteinase agents interfering with proteolytic activation of virions.


[Modern procedures in detecting viral antigens]. Besides serology and virus isolation, assays for the detection of viral antigens or nucleic acids are of increasing importance in routine diagnosis of viral infectious diseases. Critical steps, however, are the selection of suitable assays and specimens. With respect to clinical diagnosis, novel ultrasensitive methods for in vitro DNA amplification like polymerase chain reaction or ligase chain reaction are of high diagnostic significance e.g. for the demonstration of herpes simplex virus DNA in CSF samples or hepatitis C virus in patient sera.


[Poor reproducibility of parameters of heart rate variations]. The analysis of heart rate variability is supposed to be a marker of autonomic cardiac activity and is used for risk stratification of post-infarction patients. Analysis of heart rate variability in the frequency domain may permit a differentiation of vagal and sympathetic control; for such analyses only short time intervals characterized by a steady-state autonomic balance can be used. Yet, it is unclear whether single determinations of heart rate variability indices derived from short time intervals yield reproducible results. Therefore, the reproducibility of heart rate variability indices was studied with weekly measurements in 10 healthy volunteers under the following defined conditions: 13 min supine rest, 10 min standing, 13 min sitting, and 15 min cycle ergometry followed by a 14 min recovery period. Heart rate variability was determined in the frequency domain (fast Fourier transformation) and in the time domain. The reproducibility was estimated by the coefficient of variation (CV). Additionally, the reproducibility of heart rate, blood pressure, and the expiratory-inspiratory ratio of heart rate was determined. The reproducibility of the frequency domain indices (36.6-74.9% CV) and of the time domain indices (19.6-32.8% CV) was considerably worse than that of heart rate (5.2-8.2% CV), blood pressure (5.1-8.2% CV) and the expiratory-inspiratory ratio of heart rate (4.6% CV). The reproducibility of heart rate variability indices was not improved by orthostatic or ergometric challenge. This poor reproducibility does not permit a reliable interpretation of heart rate variability on the basis of single measurements in healthy volunteers. Given the wide range and scatter of the measured parameters, the diagnostic and prognostic value of heart rate variability indices derived from short recording periods appears questionable.


Comparison of capsid protein VP1 of the viruses used for the production and challenge of foot-and-mouth disease vaccines in Spain. A significant frequency of amino acid substitutions, that affect important antigenic sites on capsid protein VP1, has been found among viral preparations used for the production and for challenge, in protection assays, of foot-and-mouth disease (FMD) vaccines. The amino acid substitutions present in one of the viruses studied abolished its reactivity with two neutralizing monoclonal antibodies that recognized different epitopes on VP1. Thus, the results obtained illustrate the high potential for antigenic variation introduced by the multiple cycles of growth usually undergone by the strains used for the production and challenge of FMD vaccines.


Construction of synthetic immunogens: use of T- and B-cell epitopes of CS and RESA proteins of Plasmodium falciparum. An invariant T-helper epitope of the sequence ENDIEKKICKMEKCSSVFNV (residue no. 376-395) from the circumsporozoite (CS) protein was coupled chemically with the repeat sequences, namely (EENV)2, EENVEHDA and DDEHVEEPTVA, of ring-infected erythrocyte surface antigen (RESA) protein of Plasmodium falciparum. The CS sequence was tested for helper and proliferative activity in five inbred strains of mice of different haplotypes. The CS peptide showed dose-dependent lymphocyte proliferative response in all the strains tested. On the other hand, no proliferative response was observed with the dimers of the three RESA repeat sequences. The antibody levels in these strains immunized with RESA-CS hybrid structures showed high titres and a booster effect during subsequent immunization. Such a phenomenon was not observed with RESA peptides alone. The above CS sequence could be an ideal T-helper epitope which can be linked to hydrophilic B-cell epitopes of the RESA sequence to overcome major histocompatibility complex restriction in the host.


[Palliative minimally invasive therapy in inoperable elderly patients]. The results of palliative endoscopic therapeutic maneuvers in patients over 80 years of age were retrospectively analyzed, covering a time period of 26 months. Aims of the therapeutic modalities were the recanalization of stenoses of the gastrointestinal tract, the long-term enteral nutrition or the abolition of a malignant obstructive jaundice. Appropriate procedures were combined bougienage and laser therapy, implantation of esophageal bridging tubes, percutaneous endoscopic gastroenterostomy (PEG), and the implantation of biliary endoprosthesis after endoscopic papillotomy. We evaluated (during the period January 1, 1990 until February 29, 1992) a total of 89 patients with various diseases, all of whom, at the time of examination, were candidates for surgery, either due to the extent of a tumor or due to a significant reduction of the physical status. The complication rate of the procedures of 2.9%, and the lethality risk of 0.9% showed no increase compared to patients of younger age. Therefore, minimal invasive endoscopic therapeutic procedures are strongly indicated in inoperable patients suffering from various diseases. Symptoms may be eliminated or significantly reduced with a few procedures which can be repeated many times.


Saccharomyces cerevisiae contains a homolog of human FKBP-13, a membrane-associated FK506/rapamycin binding protein. FKB2 encodes a homolog of human FKBP-13, a membrane-associated binding protein for the immunosuppressants FK506 and rapamycin. FKB2 is located on the right arm of chromosome IV and contains an open reading frame of 135 amino acids, of which the first 17 residues comprise a putative hydrophobic leader peptide. Yeast FKBP-13 is homologous to human FKBP-13 (52% amino acid identity) and to FKBP-12, the major cytosolic receptor for FK506. In the alignment of FKBP-13 and FKBP-12 sequences, there are 28 invariant residues. Among these conserved residues are those that comprise the drug binding and peptidyl-prolyl cis-trans isomerase active site of FKBP-12. The phylogenetic conservation of the FKBP family suggest that the proteins are involved in a basic cellular function.


Antibodies directed against a yeast carboxyl-terminal peroxisomal targeting signal specifically recognize peroxisomal proteins from various yeasts. The carboxyl-terminal tripeptide Ala-Lys-Ile is essential for targeting Candida tropicalis trifunctional enzyme (hydratase-dehydrogenase-epimerase) to peroxisomes of both Candida albicans and Saccharomyces cerevisiae (Aitchison,J.D., Murray, W.W. and Rachubinski, R. A. (1991).J. Biol. Chem. 266, 23197-23203). We investigated the possibility that this tripeptide may act as a general peroxisomal targeting signal (PTS) for other proteins in the yeasts C. tropicalis, C. albicans, Yarrowia lipolytica and S. cerevisiae, and in rat liver. Anti-AKI antibodies raised against the carboxyl-terminal 12 amino acids of trifunctional enzyme were used to search for this PTS in proteins of these yeasts and of rat liver. The anti-AKI antibodies reacted exclusively with multiple peroxisomal proteins from the yeasts C. tropicalis, C. albicans and Y. lipolytica. There was a weak reaction of the antibodies with one peroxisomal protein from S. cerevisiae and no reaction with peroxisomal proteins from rat liver. Antibodies directed against a synthetic peptide containing a carboxyl-terminal Ser-Lys-Leu PTS (Gould, S. J., Krisans, S., Keller, G.-A. and Subramani, S. (1990). J. Cell Biol. 110,27-34) reacted with multiple peroxisomal proteins of rat liver and with peroxisomal proteins of yeast distinct from those identified with anti-AKI antibodies. These results provide evidence that several peroxisomal proteins of different yeasts contain a PTS antigenically similar to that of C. tropicalis trifunctional enzyme and that this signal is absent from peroxisomal proteins from at least one mammalian system, rat liver.


[The participation of RNA synthesis in the process of the acquisition and retention of conditioned reflexes (a study using antifeins)]. RNA-synthesizing activity of neuronal nuclei in the neocortex of rats increases after the termination of conditioning depending on the degree of learning. RNA synthesis shifts induced by propylnorantifein and the demethylated derivatives of ethylnorantifein are correlated only with the influence of the drugs on the retention but not the learning. Participation of RNA synthesis by the neurons of the neocortex in the mechanisms of long-term memory is discussed.


[Effect of long-term feeding with tryptophan-free diet on the circadian rhythm in rats]. Effects of long-term feeding with tryptophan (TRP)-free diet on the free running periods of wheel-running rhythm and the central serotonergic neurotransmission were examined in male blinded rats. Long-term feeding with TRP-free diet did not change the periods of wheel-running rhythm calculated from chi 2 periodogram but disordered its pattern, which seemed to be due to masking or entrainment effects. On the other hand, long-term TRP-free diet decreased the concentrations of TRP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in all brain regions tested; frontal cortex, hippocampus, thalamus, hypothalamus and pons. The density of 5-HT1A receptor (3H-8-OH-DPAT) binding was significantly decreased in only frontal cortex, while no significant change was observed in the density of 5-HT2 receptor (3H-ketanserin) binding in all regions. Although the mechanism of down-regulation of 5-HT1A receptor in frontal cortex is obscure, it was confirmed that TRP-free diet decreased central 5-HT synthesis and 5-HT neurotransmission. This dysfunction of 5-HT neurotransmission by TRP-free diet is suggested to make the circadian rhythm pacemaker susceptible to subtle environmental factors by lowering its intensity.


[Psychogenesis of the course of Sudeck's disease--a case report]. Several authors have already pointed out the significance of personality, subjectively stressful life events and relevant conflicts for the course of reflex sympathetic dystrophy. Psychodynamic hypotheses are demonstrated by two patients who had psychotherapeutic treatment and were observed over a longer stretch of time. A therapeutic concept which is enriched by this knowledge may obtain the patients' better compliance with orthopaedists, surgeons and physiotherapists and may influence duration of illness and treatment results favorably.


[The effect of Shigella sonnei strains opposite in their virulence on different links in the immune system]. For the first time different action of S. sonnei strains, opposite in their virulence, on hematopoiesis and the functional activity of T- and B-lymphocytes has been shown. The hematopoiesis-disturbing action of virulent shigellae is manifested by their capacity, more pronounced than similar capacity of an avirulent (vaccine) strain, for stimulating the processes of endo- and exocolony formation, the proliferation of hematopoietic stem cells and their migration to the blood. The effect produced by shigellae on T-cell-mediated immune response is manifested by the suppression of macrophage migration and its subsequent activation, whose manifestations and duration depend on the virulence of S. sonnei strains under study. The modulating effect of S. sonnei on B-cell-mediated immune reactions is manifested by the inhibiting action of S. sonnei virulent strain and the stimulating action of S. sonnei vaccine strain on the formation of antibody-producing cells synthesizing S. sonnei lipopolysaccharide antibodies shortly after the injection of shigellae. The results of this study indicate that S. sonnei virulent and avirulent (vaccine) produce multifunctional and differing effects on cell-mediated immune reactions, these processes being dependent on the virulence of shigellae and their individual specific antigens.


[Antibody avidity in candidiasis patients]. The properties of antibodies to Candida albicans in healthy persons, candidiasis patients and patients with somatic pathology of nonmycotic genesis were studied. Healthy persons were found to have the highest avidity of antibodies at the minimal neutralizing dose of the antigen. In all groups the titers of antibodies were inversely related to their avidity.


Surgical treatment of post-traumatic defects of the soft tissues of the head with necrosis of the calvarial bones. Experience with the treatment of patients with defects of the soft tissues of the head and necrosis of the calvarial bones has been generalized. Results of treatment using multiple craniotomy, osteonecrectomy and various methods of dermatoplasty aiming at restoration of the skin cover are discussed. The methods of treatment focused on the preservation of osteonecrotic parts and thus the hard integument of the calvaria ensuring prevention of intracranial suppurative complications, creation of a full-value skin cover, a more favourable outcome of injury and work ability of the patients are discussed and recommended.


Rationale for the need to employ a conservative method in the treatment of patients with dystrophy of the hand. Radioimmunoassay determining sexual hormone levels, functional state of the autonomic nervous system and blood supply, were used to study the causes aiding the development of dystrophies of the hand in women. All these conditions were found to be associated with gross disorders of the endocrine system, autonomic dysfunction and changes in the system of blood supply. The results were used to develop a policy for the selection of the therapeutic method and its timing with a favourable effect.


Age-dependent changes in the size of the upper lip in Bulgarians. Age-dependent changes in the width and height of the upper lip were studied in 2,300 healthy Bulgarians aged from 3 days to 102 years, for the purposes of cheiloplasty in surgery and of visual art. It has been established that at the moment of birth, the upper lip is one of the most developed organs of the human body in both sexes and that it grows in size up to the age of 80 years, completing its intensive growth during the pre-school age while in the years of puberty it does not show the growth jump characteristic of the organism as a whole. In the males, the lip remains larger during the whole period of postnatal ontogenesis except for the early childhood; the difference in the height is most expressed (3.08 mm) in the 9th decade, and in the width (5.24 mm) even later. The conclusion has been drawn that cheiloplasty can be performed at any age including the first days after birth, the dimensions obtained at the age intervals under study serving as standards.


Repair of anterior secondary palate fistula using tongue flaps. Seventy-two cases of palatal fistulae are presented. The location on anterior part of secondary palate is due to lack of double layer closure. Vascular pattern of tongue is detailed. Operative details of using tongue flap as oral layer in closure of fistula are described. Undue mobility of tongue and prevention of breakdown of tongue flap repair incidence of which is low in present series are mentioned. It is suggested as excellent method of closure of palatal fistulae in difficult cases.


Treatment of donor sites--calcium alginate versus paraffin gauze. In the surgery of burns a good healing of donor areas is essential. A controlled trial of 17 cases is presented. Mirror-image donor areas in the same patient were treated on one leg with a traditional dressing of paraffin gauze, Jelonet, on the other leg with Kaltostat, a calcium sodium alginate wound dressing. Healing time, haemostasis, ease and comfort with removal, dressings, infection and quality of the regenerated skin, were estimated. The Kaltostat dressing seemed to be superior due to the quality of the re-epithelialized donor site, the haemostatic quality and the ease and comfort with removal. There was a marginal profit in healing time.


Micrognathia in myasthenia gravis case report. Micrognathia is a disease which can appear in patients with myasthenia gravis. If patients with MG are adequately neurologically prepared they may undergo aesthetic, functional operation, which leads to improvement in the course of the disease.


Effects of acute isovolemic hemodilution and anesthesia on regional function in left ventricular myocardium with compromised coronary blood flow. The effects of progressive, isovolemic hemodilution using Dextran 70 and the effect of halothane (0.7, 0.9, 1.1, and 1.3% end-tidal, administered randomly at each level of hemodilution) on global cardiovascular and regional LV contractile functions were investigated in 24 dogs with induced critical constriction of the left anterior descending coronary artery (LAD). Two additional groups of six dogs each (with and without LAD stenosis) not undergoing hemodilution served as time controls. Regional LV contractile function was assessed by sonomicrometry in the flow-compromised apical LAD territory, as well as in three non-compromised LV areas supplied by the left circumflex coronary artery. Regional myocardial function was found to be stable throughout the study period of 4-5 h in both time control groups. Mean arterial and coronary perfusion pressures as well as LV dP/dtmin decreased (P < 0.01) during hemodilution. LV dP/dtmax remained unchanged, and heart rate and LVEDP increased slightly (P < 0.05). Systolic shortening (SS) in the LAD territory was unchanged at a hematocrit (HCT) of 33.5 +/- 0.3% (mean +/- s.e. mean), and decreased marginally at an HCT of 24.2 +/- 0.1% (SS of 17.4 +/- 1.0% as compared to 20.2 +/- 1.6% at critical constriction (CC), P < 0.05). No increase in post-systolic shortening (PSS) occurred in the compromised area. Severe LAD dysfunction was observed in the LAD territory at an HCT of 14.9 +/- 0.1%, as systolic shortening decreased (11.8 +/- 1.1%, P < 0.01 vs CC) and PSS increased (31.2 +/- 3.4%, P < 0.01 vs CC). The effects of hemodilution on global cardiovascular and regional myocardial functions were unaffected by halothane.(ABSTRACT TRUNCATED AT 250 WORDS)


Distribution of calcitonin gene-related peptide and substance P-immunoreactive nerve fibers and their correlation in the periodontal ligament of the mouse incisor. The distribution of calcitonin gene-related peptide (CGRP)- and substance P (SP)-immunoreactive (IR) nerve fibers and their correlation in the periodontal ligament of mouse incisors were examined by indirect immunofluorescence. Both CGRP-IR and SP-IR thin nerve fibers were abundant in the apical and middle third of the periodontal ligament. In the lingual portion of the incisal periodontal ligament, these nerve fibers were localized in the alveolar half of the periodontal ligament and were observed as free nerve endings. No CGRP-IR and SP-IR specialized nerve endings, such as Ruffini-like corpuscles, were observed. In the labial periodontal ligament, CGRP-IR and SP-IR nerve fibers ran along the incisal axis. The distribution of CGRP-IR nerve fibers was very similar to that of SP-IR nerve fibers.


Time profile of calcium accumulation in hippocampus, striatum and frontoparietal cortex after transient forebrain ischemia in the gerbil. The topical and temporal relationship between neuronal injury and calcium loading was investigated in gerbils following bilateral carotid artery occlusion for 5 or 10 min and recirculation times from 15 min to 7 days. The association of histochemically visible calcium deposits with neuronal death was assessed by combining two calcium stains, alizarin red and arsenazo III, with conventional histological techniques. Neuronal calcium accumulation was evaluated morphometrically in the striatum, the frontoparietal cortex and the CA1 and CA4 sectors of the hippocampus. After 5-min ischemia and 1-2 days of recirculation numerous calcium-containing neurons appeared in the CA4 sector but only a few were present in the CA1 sector. After 4 days of recirculation calcium accumulation was visible in the whole CA1 sector and the dorso-lateral part of striate nucleus. After 10-min ischemia calcium accumulation started in these regions, as well as in the cortex, already after 1 day. In the CA1 sector calcium accumulation followed a typical time course: on day 2 only the lateral parts were affected, while on day 4 the whole CA1 neuronal band was calcium positive. The regional distribution of histological lesions matched that of calcium loading and, furthermore, the lesions appeared after a corresponding delay in the respective regions. Morphometric evaluations of calcium staining and histological lesions in the CA1 sector revealed a high correlation, indicating that calcium accumulation and neuronal death are closely associated both topically and temporally. This suggests that disturbances of calcium homeostasis such as those measured by this histochemical technique are the consequence of and not the reason for ischemic cell death.


A randomized, double-blind, placebo-controlled study of dextran/pentoxifylline medication in acute acoustic trauma and sudden hearing loss. The effectiveness of any therapy in acute acoustic trauma or sudden hearing loss of unknown origin has not been demonstrated convincingly. The assessment is difficult because of a relatively high rate of spontaneous recovery. Nevertheless, many different forms of treatment are recommended. We tested one form, treatment with rheoactive substances, in a prospective, randomized, double-blind trial and compared treatment with (a) infusions of dextran-40 with pentoxifylline, (b) saline infusions with pentoxifylline, and (c) saline infusions with placebo medication. Pure-tone hearing thresholds served as control parameters and were taken before treatment and at 1 and 4 weeks after the onset of therapy. Three hundred eighty-two patients were included in the trial, 331 (87%) could be analyzed, 184 patients were treated because of sudden hearing loss, 147 because of acute acoustic trauma. The three treatment groups were comparable in their basic characteristics including the amount of initial hearing loss. In patients with sudden hearing loss, no significant differences of hearing recovery were detected between the three treatment groups. Hearing recovery was also similar in patients with acute acoustic trauma. A power analysis of the study revealed that possible true treatment differences of a hearing recovery of 10 dB would have lead to significance with a probability of over 90%. It is concluded that there were, in fact, no clinically relevant differences in hearing gains of sudden hearing loss or acute acoustic trauma between treatments with saline infusions together with placebo medication and treatment with dextran-40 and/or pentoxifylline.


Neochondrogenesis in the septal area after submucous cartilaginous resection. The present work was carried out to study cartilaginous repair after subperichondrial resection of the septal cartilage, the fibrous layer of the perichondrium remaining "in situ". In these conditions, after granulation tissue formation, both neochondrogenesis and connective tissue differentiation were observed. Neochondrogenesis was found in defect areas next to the resection borders, and connective tissue formation in those further away. The transition zone between both types of newly-formed tissues showed cells with intermediate characteristics of chondrocytes and myofibroblasts. The findings provide safer proof that new chondrocytes and fibroblasts growing after septal cartilage removal originate largely from a common precursor cell either in the fibrous perichondrial layer or in the connective tissue surrounding it. The peculiar topographic distribution of the newly-formed tissues may be explained by the different effects during respiration of mechanical forces on the septal space, which lacks its cartilaginous support, and on the adjacent remaining cartilage, as well as on the borders of both.


Study on the dye leakage response of nasal mucosa following topical, capsaicin challenge in guinea pigs. We examined the serial changes of intravenously applied dye leakage and preliminary examined histamine release into nasal lavage fluid after topical stimulation with capsaicin in guinea pigs. A significant increase in the dye leakage response was detected for 30-40 min, with the maximum response occurring between 5 and 10 min after topical capsaicin stimulation. The dye leakage response to nasal capsaicin challenge was abolished by pretreatment with topical lidocaine, general substance P analogue, topical or general high dosage capsaicin. The dye leakage response to topical capsaicin challenge was significantly reduced following pretreatment with antihistamine, diphenhydramine or atropine sulfate, although it was not affected by pretreatment with an anti-leukotriene, FPL 55712. Topical methacholine challenge did not induce a dye leakage response. An increase in the concentration of histamine in the nasal lavage fluid was noted at 5 min after topical capsaicin challenge. The concentrations of released histamine tended to be positively correlated with those of leaked dye in the nasal lavage fluids. The histamine release induced by topical stimulation with capsaicin tended to be reduced following general and topical pretreatments with high dosage of capsaicin, and was almost completely abolished following atropine pretreatment. From this study it was concluded that nasal capsaicin stimulation can reflexively induce an intravenously applied dye leakage into the nasal cavity, and that C-fiber related cholinergic nerve reflex and histamine release might, at least partially, be related to this response.


Sialomucin in middle ear cholesteatoma perimatrix. Mucosubstance histochemistry of human middle ear cholesteatoma revealed that sialomucins are abundant and sulfomucins present in small amounts in the glandlike structures of the cholesteatoma perimatrix. Based on the study, various glycoproteins were injected into the dermis of the external ear canal and infiltrated into the tympanic membranes of guinea pigs. Tympanic membranes were obtained 7 days later and light- and electron-microscopically studied. Injection of a sialomucin from bovine submaxillary gland resulted in marked proliferation of epidermis and degeneration of the lamina propria. Asialomucin prepared from sialomucin by hydrolysis produced mild thickening of the epidermis but the lamina propria was not degenerated. Fetuin and bovine serum albumin did not cause proliferation of the epidermis. Cholesterol granuloma formed in some of the specimens injected with sialomucin. The presence of sialomucin in cholesteatoma perimatrix and these experimental studies using tympanic membranes of guinea pigs suggests that sialomucins participate in the proliferation of epidermis and degeneration of subepidermal connective tissue in human middle ear cholesteatoma.


The effect of arachidonic acid metabolites on the ciliary beat frequency of human nasal mucosa in vitro. Using computerized microphotometry, we studied the effects of prostaglandin E2 (PGE2), the prostacyclin analog Iloprost, and the thromboxane A2 analog U46619 on the ciliary beat frequency (CBF) of human nasal mucosa. Thirty-two normal subjects underwent nasal cytologic brushing of the inferior meatus to obtain ciliary samples, and a total of 5,640 ciliated cell clusters were analyzed. Each subject served as their own control. PGE2, 10(-10) to 10(-6) M, produced a significant dose dependent increase in CBF of up to 12% versus control. This increase was not significantly inhibited by the addition of the cyclooxygenase inhibitor indomethacin (10(-6) M). Iloprost, 10(-12) to 10(-6) M, also significantly increased CBF by 12.7% at 10(-8) M. This ciliostimulatory effect, however, was abolished by indomethacin. The thromboxane A2 analog, 10(-10) to 10(-6) M, did not significantly effect CBF. The present study demonstrates that a thromboxane A2 analog has no effect on ciliary motility, PGE2 has a direct ciliostimulatory effect, and a prostacyclin analog has a ciliostimulatory effect likely mediated by stimulation of the cyclooxygenase pathway within human cells.


Effects of capsaicin desensitization on nasal allergy-like symptoms and histamine release in the nose induced by toluene diisocyanate in guinea pigs. Intranasal application of toluene diisocyanate (TDI) induced nasal allergy-like symptoms of sneezing and watery rhinorrhea and decreased the histamine content of the nasal mucosa in guinea pigs. However, in the animals pretreated with capsaicin (capsaicin desensitization) before sensitization with TDI, nasal allergy-like symptoms were not induced. Capsaicin desensitization also inhibited histamine release in the nasal mucosa induced by TDI. These findings suggest that antidromic impulses of capsaicin-sensitive sensory nerves stimulated by TDI cause histamine release from mast cells in the nasal mucosa, resulting in nasal discharge and sneezing in guinea pigs. Thus neurogenic inflammation via an axon reflex in the nose may contribute to the pathogenesis of vasomotor rhinitis.


Long-term hypoxia induces changes in the substance P immunoreactivity pattern in laryngeal nerve paraganglia. We previously showed that long-term hypoxia increases the dopamine content in rat laryngeal nerve paraganglia. In the present study paraganglia of rats exposed to hypoxia (10 +/- 0.5% O2) for 14 days were examined immunohistochemically to detect changes in the expression of neuropeptides and catecholamine-synthesizing enzymes. Hypoxia induced an intense cellular substance P (SP)-like immunoreactivity (LI) in some paraganglia and an increase in the number of stromal nerve fibers showing SP-LI in others. The patterns of tyrosine hydroxylase-, dopamine-beta-hydroxylase-, phenylethanolamine-N-methyltransferase-, vasoactive intestinal polypeptide-, neuropeptide-Y and calcitonin gene-related peptide-LI were not changed in response to hypoxia. The results show that hypoxia induces changes in the pattern of SP immunoreactivity in laryngeal nerve paraganglia and may indicate that SP plays a role in the regulation of catecholamine metabolism in this tissue.


A case of mixed-type dysgerminoma with a high serum concentration of both human chorionic gonadotropin and alpha-fetoprotein in a child. Dysgerminoma is divided into two types: pure and mixed. The mixed type is related to other various elements of germ cell tumors. We experienced a case of mixed type dysgerminoma with a high serum concentration of both human chorionic gonadotropin and alpha-fetoprotein. The patient was a 6 year old girl who was admitted to the Hamamatsu University School of Medicine with an abdominal mass. Laboratory investigations revealed elevated serum alpha-fetoprotein and high concentration of serum beta-human chorionic gonadotropin. The tumor originated from the left ovary. The histopathological diagnosis was dysgerminoma. Serum human chorionic gonadotropin and alpha-fetoprotein levels were useful markers in monitoring the response to treatment in this patient.


[Studies on polypeptides. IX. Synthesis and antigen specificity of pre-S region fragments of hepatitis B surface antigen]. Seven peptide fragments of HBsAg Pre-S region have been synthesized by liquid phase and solid phase methods. All peptide fragments were linked to protein carrier by carbodiimide and glutaraldehyde methods. The antigen specificity of the peptide--protein conjugates was assayed by anti-HBsAg polyclonal antibodies and anti--"a" monoclonal antibody. P1 and P5 were found to have higher antigen specificity.


[Effect of carboxyethylgermanium sesquioxide on cultured normal neonatal rat myocardial cells and cells injured by isoproterenol]. The effect of carboxyethylgermanium sesquioxide (Ge-132) on cultured neonatal rat myocytes and isoproterenol injured myocytes was studied. The results showed that Ge-132 (0.01 mmol.L-1 and 1 mmol.L-1) increased the incorporation of both [3H]-TdR and [14C]-UR, reduced the membrane lipid fluidity and inhibited the release of the cytoplasmic enzyme lactate dehydrogenase (LDH). Exposure of the myocytes to isoproterenol 0.5 mmol.L-1 for 6 hours resulted in 5-fold release of LDH compared with the control. All myocytes ceased beating. Ultrastructurally, severe sarcolemmal and mitochondrial damage was evident. When the cells were pretreated with Ge-132 before the addition of isoproterenol, the increased LDH release was inhibited significantly, and preservation of beat and ultrastructure of myocytes was observed. In addition, the activity of superoxide dismutase (SOD) was elevated by Ge-132. All the effects of Ge-132 were dose-related. The results indicate that Ge-132 may improve the metabolism of cultured neonatal rat myocytes and protect myocytes from isoproterenol-induced injury.


Inhibitory effects of tetrandrine on Bay k 8644-stimulated contraction of isolated rabbit aortic strips. In the presence of KCl 19 mmol.L-1, calcium agonist Bay k 8644 0.47 mumol.L-1 elicited a strong contraction of isolated rabbit aortic strips, and this contraction was concentration-dependently inhibited by tetrandrine; but this antagonism was noncompetitive. Calcium ionophore calcimycin evoked contraction was markedly depressed by tetrandrine. The results suggested that tetrandrine might not only inhibit transmembrane influx of calcium via potential-dependent channels but also interfere with other processes related to calcium.


Semi-differential voltammetry with carbon fiber electrodes for in vivo determination of monoamine metabolites and ascorbic acid in rat corpus striatum. Carbon fiber electrodes combined with semi-differential voltammetry were used to determine endogenous monoamine metabolites and ascorbic acid (AA). These electrodes treated by a new electrochemical procedure (30 microA for 30 s, then -2 V for 10 s) showed a significant improvement on the sensitivity and selectivity. In the rat corpus striatum, these electrodes allowed a distinct separation and continuous detection of AA, 3, 4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) simultaneously. The normal striatal levels of AA, DOPAC, and 5-HIAA were found to be 168.2 +/- 19.5, 21.4 +/- 3.9, and 3.3 +/- 0.5 mumol.L-1. Our method is credible for detecting the changes of monoamine metabolite contents induced by pharmacologic manipulations.


Different ion channel mechanisms between low concentrations of capsaicin and high concentrations of capsaicin and nicotine regarding peptide release from pulmonary afferents. Vagal nerve stimulation (1 Hz for 1 min), capsaicin (10(-8) M and 10(-6) M), resiniferatoxin (3 x 10(-10) M) and nicotine (10(-4) M) evoked a non-cholinergic bronchoconstriction in the isolated perfused guinea-pig lung preparation. Simultaneously there was an increase in the perfusate levels of calcitonin gene-related peptide-like immunoreactivity, suggesting release from sensory nerves. Both the bronchoconstriction and peptide release evoked by a low concentration of capsaicin (10(-8) M) and that evoked by nerve stimulation were depressed by tetrodotoxin, suggesting involvement of Na+ channel dependent depolarization. Since the effects of capsaicin (10(-8) M) and vagal nerve stimulation were inhibited by omega-conotoxin but not influenced by nifedipine, the Ca(2+)-channel dependent is probably of N-type. Furthermore, the capsaicin analogue resiniferatoxin also evoked omega-conotoxin sensitive peptide release and bronchoconstriction. At the higher capsaicin concentration (10(-6) M), the functional response was only slightly inhibited by omega-conotoxin or tetrodotoxin indicating that capsaicin at this concentration evoked peptide release and functional effects through other mechanisms, probably involving Ca2+ fluxes in the non-selective cation channel associated with the proposed capsaicin receptor. The nicotine (10(-4) M) evoked peptide release and bronchoconstriction were only marginally influenced by omega-conotoxin or tetrodotoxin. It is concluded that the ion-channel mechanisms underlying the peptide releasing properties of antidromic nerve stimulation and low concentrations of capsaicin are similar and depend on action potential propagation, whereas capsaicin in high, toxic concentration and nicotine mainly act via receptor operated channels.


Block of potassium outward currents in the crayfish stretch receptor neurons by 4-aminopyridine, tetraethylammonium chloride and some other chemical substances. The effects of 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on the outward potassium currents in the rapidly and slowly adapting stretch receptor neurons (SRNs) of the crayfish (Pacifastacus leniusculus) were studied using a two micro-electrode voltage-clamp technique. The leakage current was not affected by either 4-AP or TEA. External 4-AP blocked the peak outward current in a dose-dependent manner (1:1 stoichiometry) with an apparent dissociation constant (Kd) of 2.3 +/- 0.2 mM (mean +/- SEM) in the slowly and 1.4 +/- 0.2 mM in the rapidly adapting SRN, the block being voltage dependent. External application of TEA resulted in a block of the steady state current enhancing the transient characteristics of the current response. The block appeared to deviate from a 1:1 stoichiometry and the apparent Kd for TEA was 9.6 +/- 3.4 mM with a cooperativity factor n = 0.43 +/- 0.03 in the slowly adapting SRN and 34.5 +/- 9.2 mM and 0.37 +/- 0.03 respectively in the rapidly adapting SRN. Low Ca2+, apamin and charybdotoxin, which are known to block Ca(2+)-dependent K-currents, had no effects on the outward current as was also the case with catechol. It is concluded that the different effects of TEA and 4-AP on the outward current in the two types of SRNs can be explained by the presence of at least two, probably heteromultimeric, channel populations having similar sensitivity to 4-AP but different sensitivity to TEA. One channel has a high affinity (Kd = 0.8-1.6 mM) for TEA and the other a low affinity (Kd = 173-213 mM) for TEA. The low-affinity channel seems to dominate in the slowly adapting SRN while both channels are equally common in the rapidly adapting SRN. Further, the present results do not support the existence of a macroscopic Ca(2+)-dependent K+ current in the SRNs.


Functional effects of a hyperpolarization-activated membrane current in the lobster stretch receptor neurone. The functional effects of a hyperpolarization-activated membrane current (IQ) in the slowly adapting lobster stretch receptor neurone were investigated. From comparisons between changes in membrane excitability due to blockage of IQ by Cs+, in normally impaled and native unimpaled (Edman et al. 1987 b) cells, it could be concluded that the resting voltage of native cells is distinctly more negative than -65 mV (average membrane voltage of impaled cells) and, therefore, under the control of an activated IQ. Starting from this conclusion, impaled cells were polarized to holding (resting) voltages around -75 mV and their polarization and excitability properties studied after tetanic impulse activity and variation of various external influences (K+, pH, temperature), both in control conditions and after blockage of IQ by 2 mM Cs+. It was found that an unblocked IQ (a) greatly accelerates the initial (90%) decay of post-tetanic hyperpolarization, and (b) depresses distinctly any polarization and excitability alterations due to increases in extracellular K+ concentration (from 2.5 to 10 mM), variations in extracellular pH (between 6.4 and 8.6), and changes in temperature (between 14 and 24 degrees C). It was inferred that in well polarized cells, IQ plays a role as a stabilizer of membrane polarization and excitability in conditions of varying external influences. From a model study of IQ it could be concluded that, with its slow dynamic responses, the current is well adapted to its functional purposes and to the rather slow homeostatic effects of the cell's Na-K pump.


Establishment and characterization of a cell line, KaMi, from human lung large cell carcinoma. A cell line of human lung large cell carcinoma (LCC) was established directly from the metastatic skin tumor tissue. The clinical course of the patient who carried this carcinoma was peculiar; generalized lymphadenopathy, histologically resembling Hodgkin's disease, was found as the first clinical symptom. The lung tumor was not discovered until the time of autopsy. This cell line (KaMi) grew adherent to culture vessels with the population doubling time of 20.6h, formed colonies in soft agars with efficiency of 22.6%, and formed tumors in athymic nude mice. The authenticity of KaMi was confirmed by chromosomal analysis and isoenzyme patterns. KaMi cells bore a strong resemblance to the original tumor cells which were composed of small spindle cells, large polygonal cells, and multinucleated giant cells. Immunohistochemically, KaMi cells showed a weak tendency to differentiate to squamous cells, and these immunohistochemical reactivities were almost compatible to those of the original tumor cells, but ultrastructurally, KaMi cells were more immature than the original ones. Treatment with several reagents could not augment a differentiation of KaMi cells. Cytokeratin profiles showed a tendency of squamous cell differentiation. KaMi cells may aid in elucidating the pathogenesis and biology of LCC and its relationship to other lung tumors.


Enhanced expression of complement regulatory proteins on thyroid epithelial cells of Graves' disease. Cytotoxic anti-thyroid microsomal autoantibodies are highly prevalent in sera of patients with Graves' disease, but in Graves' disease thyroid tissues rarely show destructive changes. We postulated that this might be due to membrane-associated complement regulatory proteins which protect target cells from injury by complement activation. We, therefore, investigated the expression of membrane attack complex inhibitory factor (MACIF) and decay accelerating factor (DAF) in the thyroid tissues from patients with Graves' disease, Hashimoto's thyroiditis, thyroid adenocarcinoma and normal human thyroid tissues. We found a high level of expression of MACIF and DAF in Graves' thyroid tissues. Using the membrane immunofluorescence and cell-ELISA techniques, we also investigated the factors which enhanced the MACIF and DAF expression in cultured thyroid cells. Thyroid stimulating hormone, phorbol 12, 13-dibutyrate and thyroid stimulating autoantibody enhanced the MACIF and DAF expression. These findings suggest that the membrane complement regulatory proteins increase in response to the thyroid stimulating factors such as thyroid stimulating autoantibody in Graves' disease and that this increase then protects the cells from damage due to complement activation by thyroid autoantibodies.


Hepatitis C virus antibody titration in patients with chronic hepatitis C, before and after interferon treatment. We measured hepatitis C virus antibody titers in 13 patients with chronic hepatitis C to determine whether titration of hepatitis C virus antibody was useful or not, to predict and evaluate the efficacy of interferon (IFN) treatment. During administration of IFN, hepatitis C virus titers declined in all patients. Antibody titers performed before treatment as well as just at the end of treatment did not correlate with change of the alanine aminotransferase levels during administration of IFN. Antibody titers declined continuously after treatment in 5 patients with normal alanine amino-transferase levels for over 6 months after discontinuation of IFN. Antibody titers rose again in 6 patients whose alanine aminotransferase levels fluctuated after treatment. An exceptional pattern of change occurred in 2 patients whose antibody titers declined continuously although their alanine aminotransferase levels fluctuated after treatment. Repeated titration of hepatitis C virus antibody appears to be useful for evaluating the long-term efficacy of IFN treatment.


Detection by western blotting of an antibody to the hepatitis C virus E1 envelope protein in sera of patients with chronic liver disease. We detected an antibody to HCV envelope protein (E1) in sera of patients with HCV-related chronic liver diseases (20 patients with chronic hepatitis and 5 patients with liver cirrhosis) by Western blotting using the fusion protein of E1 envelope protein and beta-galactosidase as an antigen. The antibody to HCV E1 (anti-HCV E1) was detected in 8 (42%) of 19 patients positive for HCV-RNA (16 were positive and 3 were negative for antibody to C100-3) and in 1 (17%) of 6 patients negative for HCV-RNA but positive for antibody to C100-3. HCV-RNA was detected in 8 (89%) of 9 anti-HCV E1 positive sera. The value of alanine aminotransferase was significantly higher in patients positive for anti-HCV E1 than in patients negative for the antibody. Although an antibody to the envelope protein of HCV is suspected to be one of the candidates of virus-neutralizing antibodies, our results suggest this hypothesis appears to be unlikely.


[Preoperative estimate of the weight of prostatic adenoma using abdominal echography]. Using a sample of 41 patients, diagnosed with prostate adenoma, an estimate was made on the degree of correlation between the weight of the adenoma as predicted through abdominal ultrasound scan (x) and the actual weight after surgical removal (y). An experimental principle or mathematical formula has been worked out to translate that correlation and it allows the urologist to appraise the adenoma's actual weight as related to the ultrasound scan weight. The degree of correlation between the ultrasound-estimated weight and the actual weight was high (0.85) and statistically significant (p < 0.01). The experimental principle of mathematical formula which will allow the urologist to make a closer approximation to the actual weight of adenomas studied by ultrasound was y = 0.93 * x + 4.7.


Ion channels for the mechano-electrical transduction and efferent synapse of the hair cell. Auditory and vestibular information is applied to the hair cell hair bundle as mechanical energy, and is transduced into electrical energy by gating ion channels. The m-e.t. channel has a unitary conductance of 50 pS and a broad selectivity to monovalent cations and to divalent cations. Ca ions are the most permeable through the channel. The angular displacement of the hair bundle is the primary gating factor. Circumstantial evidence indicates the possibility of the direct gating of channels by the membrane deformation itself. The transduction potential activates voltage gated Ca channel and leads to the release of neurotransmitters which activate afferent neurones. Cholinergic muscarinic receptors likely mediate the inhibitory efferent innervation to the hair cell.


Nerve growth factor chromatin receptor and cell surface receptor-regulated growth of melanocytes and nevus cells. RNA synthesis in melanocytes and nevus cells, and the proliferation of those cells in the presence of nerve growth factor (NGF) and 12-0-tetradecanoyl-phorbol-13-acetate (TPA), were found to correlate with the amount of NGF bound to the chromatin versus the total internalized NGF (n/c NGF = nuclear/cellular ration). In nevus cells and in melanocytes of the early passages (n/c NGF = 0.16-0.18), NGF slightly activated RNA synthesis but was without any effect on cell growth. At passage 5-6 of melanocytes (n/c NGF = 0.88), NGF inhibited RNA synthesis, which led to inhibition of cell growth. Removal of TPA from the culture of nevus cells resulted in increased n/c NGF ratio and in a switch from activatory to inhibitory action of NGF. The possibility that the cell surface receptor mediated the stimulatory effect of NGF and may antagonize the chromatin receptor-mediated inhibitory effect of NGF of melanocyte and nevus cell growth is discussed.


Control of angiogenesis by heparin and other sulfated polysaccharides. Heparin and its related polysaccharides are revealed to have important new functions as regulators of blood vessel growth and regression. This regulatory activity may be explained in part by at least five mechanisms in which heparin and heparan sulfate interact with peptide growth factors: (1) Heparin and heparan sulfate have a high affinity for angiogenic growth factors such as the fibroblast growth factors and VEGF, as well as for angiogenic inhibitors such as thrombospondin and platelet factor 4. (2) Heparin and its related polysaccharides stabilize bFGF and other growth factors. (3) FGFs and thrombospondin are stored in the extracellular matrix bound to heparan sulfate; fragments of heparin or heparan sulfate may act as natural chaperones to shuttle bFGF or other growth factors to different cellular compartments. (5) Heparin-like low-affinity receptors on the surface of endothelial cells (and other cells), prepare FGFs for binding to their specific high affinity receptors; and (6) Heparin and its related polysaccharides potentiate angiostatic steroids. It is likely that future investigations will uncover even more fundamental regulatory roles for heparin as well as for other polysaccharides in the normal function of growth factors, especially in the complex process of angiogenesis.


Actions of nitric oxide on the acute gastrointestinal damage induced by PAF in the rat. The actions of nitric oxide (NO) on the acute gastrointestinal damage induced by platelet-activating factor (PAF) have been investigated in the rat. S-nitroso-N-acetyl penicillamine, which spontaneously generates NO, dose-dependently inhibited PAF-induced gastrointestinal plasma leakage, a measure of the initiation of vascular damage. The inhibitor of NO synthase, NG-monomethyl-L-arginine substantially potentiated gastrointestinal damage and plasma leakage induced by E. coli endotoxin, but had no effect on that induced by intravenous infusion of PAF. Endogenous NO may thus have a protective role in the gastrointestinal vascular that can be mimicked by generators of NO. The protection afforded by endogenous NO may, however, be dependent on the nature of the inflammatory stimulus used to induce gastrointestinal damage.


Distribution of repetitive and non-repetitive circumsporozoite protein epitopes on Plasmodium falciparum sporozoites and immunochemical characterization of human malaria antisera. The presence and distribution of circumsporozoite protein (CSP) epitopes located in the repetitive and non-repetitive regions were studied in three Plasmodium falciparum strains, NF54, IFA5 and IFA6. It was found by immunofluorescence, Western blotting and immunoelectron microscopy that mAbs to epitopes of the repetitive domaine bound similarly to the CSP of all three strains. MAbs to epitopes of the flanking regions yielded either some strain differences (mAbs to the C-terminal end), or reacted only in immunofluorescence tests on whole sporozoites (mAbs to the N-terminal end). Human sera from an area endemic for malaria, two of them positive in ELISA on (NANP)40 and two negative, were tested for their reactivity with epitopes of the flanking regions of the CSP. The presence of antibodies to such epitopes could be demonstrated by Western blots and immunocytochemistry independent of the reactivity of the sera to recognize (NANP)40. All tested bound to salivary gland tissues but not to their secretory product in immunocytochemical experiments.


Analysis of internal proteins of influenza A (H2N2) viruses isolated from birds in East Germany in 1983. Proteins and RNAs of influenza A (H2N2) viruses isolated from birds in 1983 in East Germany were compared antigenically with those of H2N2 human strains. The electrophoretic mobility of the viral proteins and of the S1-treated double-stranded RNAs from two human and six avian strains, as well as the results of EIA-tests using monoclonal antibodies to their matrix protein and nucleoproteins indicate an antigenic relationship between the avian isolates and human strains of H2N2 subtype. One of the avian strains had a reduced amount of matrix protein.


Effect of natural and synthetic immunomodulators on the synthesis of interferon by peritoneal cells of mice. The effect of different natural and synthetic immunomodulators on the spontaneous interferon (IFN) synthesis by freshly isolated resident peritoneal cells of BALB/c, NZB and C3H mice was investigated. Actinomycetal glycolipids isolated from Curtobacterium betae, Faenia rectivirgula, Rothia dentocariosa and Saccharopolyspora hirsuta at the concentration 1-20 micrograms/ml were found to potentiate the IFN synthesis by the peritoneal cells of BALB/c mice. Similar results were obtained when dsRNA, LPS of Shigella sonnei and lipid A isolated from the LPS were used. The effect of potentiation of the physiological IFN production by the immunomodulators was observed also in the cells of C3H and NZB mice. In contrast, the inhibition of the IFN synthesis was observed when the peritoneal cells of BALB/c and NZB mice were treated with imuthiol at concentration 0.1-10 micrograms/ml. Thymomodulin (TFX-Polfa) at concentration of 1-100 micrograms/ml had no effect on the spontaneous IFN production.


Recombinant interferon-alpha 2 inhibits HIV replication in chronically infected promonocytic cells. Promonocytic cells U937 with previously established HIV-1 persistent infection, were treated with increasing doses of the recombinant INF-alpha 2. This resulted in a significant decrease of virion-associated reverse transcriptase levels in medium of the cultures studied, most pronounced by the highest interferon doses, but depending on this cytokine presence. In spite of the marked restrictive effect of the interferon on the infectious virus production the synthesis, of viral structural proteins by the U937 cells, as detected by immunofluorescence, was not affected. The therapeutic index of interferon was considerably high.


Finasteride for benign prostatic hyperplasia. The pathogenesis of benign prostatic hyperplasia is related to the action of 5 alpha-dihydrotestosterone (DHT), the physiologically active form of testosterone. The conversion of testosterone to DHT is catalyzed intracellularly in prostatic tissue by the enzyme 5 alpha-reductase. Finasteride blocks the action of 5 alpha-reductase by competitively inhibiting the binding of testosterone to 5 alpha-reductase. The maximum effect of finasteride on reducing prostatic volume occurs after three months of oral therapy. Most patients experience improvement in urine flow rates, and side effects are minimal. However, following discontinuation of treatment, serum DHT levels return to baseline within two weeks.


The prevalence and prognostic significance of arrhythmias in Duchenne type muscular dystrophy. To investigate the prevalence and prognostic significance of cardiac arrhythmias in Duchenne type muscular dystrophy 24-hour ambulatory ECG was performed in 80 patients with Duchenne type muscular dystrophy, and they were followed up for 5 years. Various arrhythmias were observed in 63.8% (51 of 80) of the patients. Ventricular premature beats were found in 30% (24 of 80), and the incidence of ventricular premature beats increased as the clinical severity of skeletal muscle involvement advanced. Forty-seven patients survived for 5 years, but the incidence of arrhythmias increased from 38.3% (18 of 47) to 74.5% (35 of 47) (p < 0.001). During the 5-year period, four of 33 deaths were sudden. Malignant ventricular premature beats (ventricular couplets, ventricular tachycardia, and R-on-T-type ventricular premature beats) were observed in three of these four patients. It appears that cardiac arrhythmias are a common complication of Duchenne type muscular dystrophy and that the incidence of ventricular arrhythmias increases with the progression of myocardial involvement. There is an association between ventricular arrhythmias and sudden death, but the reduction of ventricular arrhythmias may not reduce the incidence of episodes of sudden death.


A multicenter, randomized, controlled trial to evaluate the effect of prophylactic octreotide on ERCP-induced pancreatitis. Eight-four patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) were randomized to receive 100 micrograms of octreotide intravenously immediately prior to ERCP, and 100 micrograms subcutaneously 45 min after the initial dose, or placebo. Amylase, lipase, and glucose were measured and clinical assessment was performed before, and 2 and 24 h after, ERCP. We define clinical pancreatitis as the combination of elevated amylase or lipase with abdominal pain and tenderness. Interim analysis in 84 patients revealed an 11% incidence of clinical pancreatitis in the control group and 35% in the treatment group (p < 0.01). There were no differences in either group with respect to sphincterotomy, gender, age, duration of ERCP, number of cannulations of the pancreatic duct, degree of duct injection, or the volume of contrast injected. Analysis of group differences stratified by sphincterotomy revealed the following: 1) In patients who did not undergo a sphincterotomy, there was a significantly higher rate of pancreatitis in the treatment group [10/17 (59%) versus 1/17 (6%) RR 10.0 (95% CI 1.4-69.8)]. 2) Sphincterotomy reduced the rate of pancreatitis in patients who received octreotide from 10/17 (59% no sphincterotomy), to 3/20 (15% sphincterotomy) (p = 0.01), which equals the rate in patients who received placebo and underwent sphincterotomy [4/25 (16%)]. 3) Although the incidence of pancreatitis was higher in the treatment group, octreotide may reduce the severity of pancreatitis measured by the number of days NPO (Wilcoxon rank sum, p = 0.02), length of stay after ERCP (p = 0.13), the number of days of pain (p = 0.11), and the degree of amylase elevation (p = 0.04). We conclude that: 1) Octreotide appears to increase the incidence of pancreatitis when given prophylactically for diagnostic ERCP. 2) Although pancreatitis was more common in the octreotide group, it was less severe than the placebo group. 3) Sphincterotomy may afford protection against pancreatitis in patients who received octreotide. 4) We cannot recommend the use of prophylactic octreotide during diagnostic or therapeutic ERCP.


Chronic and intradialytic effects of high-flux hemodialysis on tumor necrosis factor-alpha production: relationship to endotoxins. Tumor necrosis factor-alpha (TNF alpha) likely plays a role in hemodialysis-associated complications. As TNF alpha is mainly produced by monocytes in response to endotoxins, we studied its production and the presence of circulating endotoxins in patients dialyzed on polyacrylonitrile (PAN) membrane. Spontaneous production of TNF alpha was observed in patients before the dialysis session and increased during the session. Endotoxins were present in serum from patients chronically dialyzed with PAN and increased during hemodialysis session. In addition, intradialytic decrease in CD14 antigen expression on circulating monocytes, which could be caused by endotoxins, was found. The continuous presence of low amounts of circulating endotoxins between sessions may explain the chronic increase in TNF alpha secretion, while high amounts of circulating endotoxins may account for intradialytic oversecretion of TNF alpha and downmodulation of CD14. We suggest that endotoxin-free dialysates should be a prerequisite for the use of high-flux membranes.


Nonmucinous nature of the surface material of the bladder mucosa. The urinary bladder is lined by transitional epithelium, also known as urothelium. Some investigators have described a material known as mucin, which lines the luminal surface of the urothelium, but its nature is not well understood. The authors examined sections of bladder from rat, mouse, rabbit, and man and found that, although they reacted differently to common histochemical stains for complex carbohydrates, none showed any material that stained as mucin on the surface of the mucosa. Rather, intracellular granules that have varying staining characteristics in different animals were found on the luminal side of the urothelium. The authors speculate, based on their histochemical findings, that some form of mucin may be present in the urothelial granules in man and that studies on animals may not be applicable to man.


Elevated second trimester maternal serum beta-HCG concentrations and subsequent adverse pregnancy outcome. Previous studies have found an association between elevated second trimester maternal serum alpha-fetoprotein (MS-AFP), in the absence of fetal anomalies, and adverse pregnancy outcome. We studied the association between elevated second trimester maternal serum beta-HCG, now also routinely measured by prenatal screening programs, and adverse pregnancy outcome by reviewing retrospectively the pregnancy outcomes among women with markedly elevated midtrimester beta-HCG in our prenatal screening program. Seven (0.23%) of 3,000 consecutively screened women had a serum beta-HCG above 5 MOM. Four (57%) of these 7 women had an adverse pregnancy outcome including severe preeclampsia (n = 2), abruptio placentae (n = 1), or preterm labor (n = 1). A concurrently elevated MS-AFP was found in only one of these 4 patients. Elevated mid-trimester maternal serum beta-HCG may be an independent risk factor for subsequent adverse pregnancy outcomes.


Deletion of the KIT and PDGFRA genes in a patient with piebaldism. We have previously shown that human piebaldism results from mutations of the KIT gene, which encodes the receptor for the mast/stem cell growth factor and is located in chromosome segment 4q12. Using DNA of a patient with piebaldism, mental retardation, and multiple congenital anomalies associated with a 46,XY,del(4) (q12q21.1) karyotype, we carried out quantitative Southern blot hybridization analyses of the KIT gene and the adjacent PDGFRA (platelet-derived growth factor receptor alpha subunit) genes. The patient was hemizygous for both the KIT and PDGFRA genes, indicating that both of these genes are included within the deleted region. Therefore, deletion of the KIT and PDGFRA genes may account for the piebald phenotype in this patient.


Cyclooxygenase products do not modulate angiotensin II-induced contractions of human chorionic plate arteries. This study sought to determine whether cyclooxygenase products modulate angiotensin II-induced contractions of human placental arteries. Ring segments of chorionic plate arteries (3 to 5 mm inner diameter) were obtained after normal vaginal deliveries. Active force in response to 10(-6) mol/L angiotensin II or 10(-4) mol/L arachidonic acid was measured in the presence or absence of 10(-6) mol/L indomethacin to inhibit cyclooxygenase. The response of K+ contracted arteries to the stable prostacyclin analog iloprost was also tested to determine whether prostacyclin relaxes these vessels. Statistical differences were assessed by analysis of variance, Wilcoxon sign rank test, or Student t test with Bonferroni correction for multiple comparisons. Successive applications of angiotensin II produced significantly less contraction than the original dose (angiotensin II tachyphylaxis). Angiotensin II tachyphylaxis was unaffected by indomethacin. Arachidonic acid caused an indomethacin-sensitive contraction and iloprost failed to relax the arteries. These results suggest that cyclooxygenase products do not mediate angiotensin II tachyphylaxis in these vessels.


Simplified gram stain interpretive method for diagnosis of bacterial vaginosis. Two methods which only consider bacterial morphotypes and require counting various types of bacteria, for interpreting Gram stains of vaginal secretions for the purpose of diagnosing bacterial vaginosis were previously described. A new interpretative method, which combines clue cells with bacterial morphotypes as diagnostic markers, is offered. One hundred twenty patients were tested with the new interpretative method and clinical criteria of bacterial vaginosis as the reference standard. The new method was found comparable to older methods when all were compared with clinical diagnostic methods. The sensitivity of the clue cell method was 86.1% and the specificity was 92.8%. The predictive value of a positive test was 83.7% for a population with a prevalence of bacterial vaginosis of 30%. The negative predictive value was 94.0%. If clue cells are present and the nonlactobacilli morphotypes exceed lactobacilli morphotypes, bacterial vaginosis can be diagnosed without the need for exact bacterial counts.


Inhibitory effect of medroxyprogesterone acetate on angiogenesis induced by human endometrial cancer. The purpose of this study was to investigate the effect of medroxyprogesterone acetate on angiogenesis induced by endometrial cancer and to elucidate the possible mechanisms by which it inhibits the growth of the cancer. Tumors were obtained from 29 patients with endometrial adenocarcinoma, and angiogenesis was assayed in corneas of white rabbits. Transplantation of tumor tissues into rabbit corneas induced angiogenesis in 70.4% of the corneas, but their transplantation with a pellet of medroxyprogesterone acetate induced angiogenesis in only 21.5% of the corneas. This compound also inhibited angiogenesis induced by acidic fibroblast growth factor and transforming growth factor-alpha. Inhibition of angiogenesis may be one mechanism by which medroxyprogesterone acetate inhibits the growth of endometrial adenocarcinoma, and its inhibition of neovascularization induced by adenocarcinoma may be through its direct action on endothelial cells.