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M Steinhoff

Publications and source records attributed to M Steinhoff.

At least 55 records · Page 3Linked to original sources

Alpha and beta subunits of inhibin/activin as sex cord-stromal differentiation markers.

Inhibins (alpha and beta heterodimers) and activins (beta homodimers) are related peptides with opposing biologic action on gonadotropin regulation. They serve as components of the pituitary-gonadal feedback system. Although sex-cord stromal tumors can usually be distinguished from ovarian epithelial tumors or their metastases by morphology or by using antibodies against intermediate filaments, the diagnosis remains difficult in rare situations in such cases as sarcomatoid granulosa-theca cell tumors, ovarian small cell carcinomas, or soft-tissue sarcomas. A total of 28 sex cord-stromal tumors of the ovary and 43 non-sex cord-stromal tumors were immunohistochemically evaluated for the presence of alpha and beta subunits of inhibin and activin. For comparison, 10 normal adult gonads including seven ovaries with hilar regions and three testes also were examined. Immunoreactivity for both alpha and beta subunits of inhibin/activin was identified in both non-neoplastic and neoplastic granulosa, Sertoli, Leydig, hilar and luteinized theca cells, with the strongest immunoreactivity in Leydig and hilar cells. One of three Sertoli-Leydig cell tumors that showed a sarcomatoid growth pattern and one sex-cord tumor with annular tubules also were immunoreactive for both subunits. For non-sex cord stromal-derived ovarian tumors, alpha subunit immunoreactivity was negative in all but two of five ovarian mucinous tumors. Weak immunoreactivity for beta subunit was found in most ovarian surface epithelial carcinomas, two of four colonic, and one of three pancreatic carcinomas. No immunostaining was found in nonspecialized gonadal stromal or interstitial cells, thecal cells, germ cells, ovarian small cell carcinomas, carcinoid tumors, dysgerminomas, or leiomyosarcomas. Immunostaining of alpha subunit (inhibin alpha), but not of beta subunit could serve as a sex cord-stromal differentiation marker because alpha subunit alone is largely confined to sex cord-stromal lesions with the exception of some ovarian mucinous tumors. Further studies are needed to define the usefulness of this sex cord-stromal differentiation marker in the practice of surgical pathology. Coexpression of alpha and beta subunits in sex cord-stromal elements suggests that dimeric inhibin is expressed in these cells.

Activins↗

A strict requirement of interleukin-4 for interleukin-4 induction in antigen-stimulated human memory T cells.

The role of interleukin-4 (IL-4) in the induction of IL-4 in mouse T cells is well established, but conflicting results have been reported with anti-CD3-primed human T cells and T cell clones. Therefore, IL-4 regulation was investigated in short-term cultured human T cells primed in vitro with either a superantigen or a hapten, nickel sulfate (NiSO4), for 3 days and expanded with IL-2 for another 5 days. Under these conditions, antigen-specific IL-4 producing T cells were generated in 35/40 cultures. Priming for IL-4 production was abrogated in all cultures by anti-IL-4 antibody or soluble IL-4 receptor (sIL-4R). Primed T cells that were IL-4- when cultured with IL-2 only developed an IL-4 producing phenotype when primed and expanded in the presence of exogenous IL-4. T cells primed in the presence of either endogenous or exogenous IL-4 produced 10-200-fold more IL-4 than T cells primed in the presence of anti-IL-4 antibody or sIL-4R. While IL-4 induction was absolutely dependent on IL-4, neither endogenous nor exogenous IL-4 influenced IFN-gamma synthesis. Most importantly, IL-4 induced and sIL-4R abolished priming for IL-4 production even in NiSO4-specific memory T cells from sensitized individuals. Thus, IL-4 induction in antigen-specific human memory T cell populations absolutely required IL-4. The IL-4 pathway of memory T cells retained a remarkable plasticity in sensitized individuals.

Adult↗

Pneumococcal polysaccharide vaccine in children with chronic renal disease: a prospective study of antibody response and duration.

We studied the antibody response to pneumococcal serotypes 3 and 14 after pneumococcal polysaccharide vaccine was administered to 41 children with renal disease. One month after vaccination, 76% and 61% of patients achieved at least a twofold titer rise to serotypes 3 and 14, respectively; this finding was comparable to historic control values. One year after vaccination, the majority of patients retained protective antibody levels. Achieving a titer > or = 1.0 microgram/ml IgG at 1 month was highly predictive of retaining a protective antibody level > or = 0.15 microgram/ml at 1 year.

Adolescent↗

Wood-burning stoves and lower respiratory illnesses in Navajo children.

BACKGROUND: Acute lower respiratory illnesses (ALRI) have been associated with exposure to domestic smoke. To examine further this association, a case-control study was conducted among Navajo children seen at the Public Health Service Indian Hospital at Fort Defiance, AZ. METHODS: Cases, children hospitalized with an ALRI (n = 45), were ascertained from the inpatient logs during October, 1992, through March, 1993. Controls, children who had a health record at the same hospital and had never been hospitalized for ALRI, were matched 1:1 to cases on date of birth and gender. Home interviews of parents of subjects during March and April, 1993, elicited information on heating and cooking fuels and other household characteristics. Indoor air samples were collected for determination of time-weighted average concentrations of respirable particles (i.e. < 10 microns in diameter). RESULTS: Age of cases at the time of admission ranged from 1 to 24 months (median, 7 months); 60% of the cases were male. Matched pair analysis revealed an increased risk of ALRI for children living in households that cooked with any wood (odds ratio (OR), 5.0; 95% confidence interval (CI), 0.6 to 42.8), had indoor air concentrations of respirable particles > or = 65 micrograms/m3 (i.e. 90th percentile) (OR 7.0, 95% CI 0.9 to 56.9), and where the primary caretaker was other than the mother (OR 9, 95% CI 1.1 to 71.4). Individual adjustment for potential confounders resulted in minor change (i.e. < 20%) in these results. Indoor air concentration of respirable particles was positively correlated with cooking and heating with wood (P < 0.02) but not with other sources of combustion emissions. CONCLUSIONS: Cooking with wood-burning stoves was associated with higher indoor air concentrations of respirable particles and with an increased risk of ALRI in Navajo children.

Acute Disease↗

The role of pulse oximetry. Its use as an indicator of severe respiratory disease in Peruvian children living at sea level. Respiratory Group in Peru.

OBJECTIVE: To evaluate pulse oximetry as a technique for diagnosing pneumonic and nonpneumonic acute lower respiratory tract infection (ALRI) in Peruvian children. DESIGN: Children with acute respiratory infection were diagnosed with hypoxemia by pulse oximetry, with ALRI by the World Health Organization (WHO) algorithm and clinical examination, and with pneumonia by radiographic examination. Diagnoses were compared using kappa analysis. SETTING: Pediatric emergency department. PATIENTS: Peruvian pediatric patients with acute respiratory infection (n = 269) and well children (n = 162). MAIN OUTCOME MEASURES: Hypoxemia (arterial oxygen saturation < 96.6% of the mean arterial oxygen saturation of well children -2 SD). RESULTS: Children with pneumonic and nonpneumonic ALRI (59%, 160/269) had a mean (+/- SD) arterial oxygen saturation significantly lower than well children (93.8% +/- 3.5% vs 98.7% +/- 1.51%; P < .01). Pulse oximetry detected 88% and the WHO algorithm 90% of cases of pneumonic ALRI. The WHO algorithm and pulse oximetry detected 72% of radiologic pneumonia. Pulse oximetry misclassified notably fewer well children than did the WHO algorithm (4% vs 35%). Pulse oximetry and the WHO algorithm together (SATWHO) detected 99% and 87% of pneumonic ALRI and radiologic pneumonias, respectively, and both methods detected 94% of all cases of pneumonic and nonpneumonic ALRI diagnosed clinically. CONCLUSIONS: Pulse oximetry and the WHO algorithm are practical, helpful, and appropriate for use in developing countries to identify children with pneumonic and non-pneumonic ALRI who require treatment. The SATWHO is highly sensitive for detecting children with ALRI.

Acute Disease↗

Immune response to influenza vaccination in children with renal disease.

Although immunization with influenza vaccine is recommended for children with chronic renal disease and after organ transplantation, the antibody response in these children has not been well described. We studied the response to the 1993-1994 trivalent influenza vaccine in children, aged 1-21 years, with chronic renal failure (n = 15), end-stage renal disease requiring dialysis (n = 10), and post renal transplantation (n = 17). Each group's antibody response was compared with that of a control group (n = 7). No significant differences were found in seroconversion rates, percentage of patients achieving protective hemagglutination-inhibition titers post vaccination or change in geometric mean titers from pre to post vaccination between study groups and controls. These results suggest that pediatric patients with renal disease will respond and therefore will benefit from currently recommended influenza immunization.

Adolescent↗

Distribution of rat hepatic steroid 5 alpha-reductase 1 as shown by immunohistochemistry.

Peptide fragments of rat liver 5 alpha-reductase were synthesized according to the published primary sequence data. The peptide were used (i) in free form and (ii) linked to keyhole limpet hemocyanin (KLH), respectively, for immunization of rabbits. Resulting antisera showed positive reaction with the respective peptide-antigen in an ELISA. In Western blot experiments the antisera specifically recognized a 26,000 mol wt protein in extracts from female and male rat liver. All antisera, as well as isolated immunoglobulins, showed inhibition of 5 alpha-reductase activity in microsomes prepared from rat liver. Positive immunohistochemical reactions were observed in the perinuclear cytoplasm of hepatocytes. No reaction was seen in Kupffer- and connective tissue cells. Acinar heterogeneity of the immunoreaction was seen in the male rat liver with a gradient from the portal canal to the central vein. After androgen-deprivation a considerable increase in immunoreactivity was seen in male rat liver cells, indicating androgen-dependent suppression of the enzyme in male liver.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Clinical predictors of acute radiological pneumonia and hypoxaemia at high altitude.

Fast breathing has been recommended as a predictor of childhood pneumonia. Children living at high altitude, however, may breathe faster in response to the lower oxygen partial pressure, which may change the accuracy of prediction of a high respiratory rate. To assess the usefulness of clinical manifestations in the diagnosis of radiological pneumonia or hypoxaemia, or both, at high altitude (2640 m above sea level), 200 children aged 7 days to 36 months presenting to an urban emergency room with cough lasting less than seven days were studied. Parents were interviewed and the children evaluated using standard forms. The results of chest radiographs and pulse oximetry obtained after clinical examination were interpreted blind. Radiological pneumonia and haemoglobin oxygen saturation < 88% were used as 'gold standards'. One hundred and thirty (65%) and 125 (63%) children had radiological pneumonia and hypoxaemia respectively. Crepitations and decreased breath sounds were statistically associated with pneumonia, and rapid breathing as perceived by the child's mother, chest retractions, nasal flaring, and crepitations with hypoxaemia. The best single predictor of the presence of pneumonia is a high respiratory rate, although the results are not as good as those reported by other studies. A respiratory rate > or = 50/minute had good sensitivity (76%) and specificity (71%) for hypoxaemia in infants. Hypoxaemia had a good sensitivity and specificity for pneumonia mainly in infants (83% and 73%, respectively). Logistic regression analysis showed that decreased or increased respiratory sounds and crepitations were associated with pneumonia, and that hypoxaemia is the best predictor when auscultatory findings are excluded. These results suggest that some clinical predictors appear to be less accurate in Bogota than in places at lower altitude, and that pulse oximetry can be used for predicting pneumonia.

Acute Disease↗

Hormonally induced changes in apocrine secretion of transglutaminase in the rat dorsal prostate and coagulating gland.

Coagulating gland and dorsal prostate of the rat are peculiar in secreting transglutaminase, a protein-cross linking enzyme that is released in an apocrine fashion. To elucidate whether or not the intracellular pathway and the unusual extrusion mechanism proceed constitutively or were differentially regulated, transglutaminase immunoreactivity was studied both at the light and electron microscopic levels. In addition, ultrastructural morphometry and scanning densitometry were applied to quantitate hormone-dependent distribution of transglutaminase. Coagulating glands and dorsal prostate, respectively, from sexually active rats were compared to those from sexually inactive, castrated, estradiol-treated or testosterone-substituted castrated animals. In intact, sexually active animals, no labeling of the cisternae of rough endoplasmic reticulum was seen, but instead the hyaloplasm was labeled. In the supranuclear portions of the cells an increase in labeling density of the hyaloplasm subjacent to the plasma membrane was found, whereas no labeling of either Golgi stacks or vesicles was observed. Apical blebs projecting into the acinar lumen were densely labeled. In castrated animals, epithelium showed a reduction of rough endoplasmic reticulum, loss of secretory blebs, and a decrease in cell size. Morphometric analysis of immunolabeling of coagulating gland epithelium from experimental animals resulted in a highly significant reduction of labeling of the hyaloplasm and apical blebs which was reversed by testosterone supplementation of castrated animals. After estrogen treatment, the reduction in immunolabeling was less pronounced, but morphology of apical blebs was obviously changed. Results from scanning densitometry of Western blots correlated with quantitative immunoelectron microscopical findings. Northern blot analysis using a secretory transglutaminase cDNA probe showed characteristic changes at the RNA levels. Our results indicate that apocrine secretion of transglutaminase in rat coagulating gland and dorsal prostate is a hormonally controlled process, where androgen deprivation results in impaired biosynthesis and release of transglutaminase, whereas estradiol treatment only partially inhibits secretion, but changes morphological features of the glandular epithelium, especially apocrine bleb formation.

Animals↗

Arguments against the prostatic origin of the R-3327 Dunning H tumor.

The Dunning tumor, originally described as a carcinoma of the rat dorsal prostate, has for long been used as an experimental model of prostatic cancer. We have recently presented a number of morphological findings that are incompatible with the prostatic origin of the H-subline of the Dunning tumor. In this paper, biochemical and immunohistochemical markers of rat prostate and mammary gland are studied in the R-3327 Dunning H tumor. Pieces of the H tumor were inoculated in male or lactating female rats. The electrophoretic protein pattern of Dunning tumor extracts was more similar to that of the mammary gland than the dorsolateral prostate. Proteins selectively appearing after metabolic labeling in Dunning tumors grown in lactating rats corresponded to labeled proteins in mammary glands from the same animals. Secretory proteins typical of the lateral prostate (SVS II) and dorsal prostate (transglutaminase) could not be detected immunohistochemically in the Dunning tumor. Western blot studies of tumor extracts and slot blot analysis of RNA preparations from the tumor confirmed the absence of SVS II and prostate specific transglutaminase from the Dunning tumor. On the other hand, the presence of mammary gland proteins such as milk fat globule membrane proteins, lactoperoxidase and lactalbumin were detected in the Dunning tumor by immunohistochemistry and Western blotting, but were absent from the dorsolateral prostate. Transferrin-mRNA, expressed in the male urogenital tract and also in the liver and other tissues, was detected in the mammary gland and Dunning tumor, but not in the dorsolateral prostate. The absence of mammary gland secretory beta-casein in the Dunning tumor was related to the elevated Ha-ras oncogene expression in the tumor, previously reported to suppress casein expression. The findings clearly demonstrate that the prostate cannot be the origin of the Dunning tumor, presently being used in prostatic cancer research. The designation prostatic adenocarcinoma for this tumor is therefore invalid. Furthermore, the data support our view that mammary gland might be the origin of the Dunning tumor, although the derivation from the bulbourethral or the parotid glands cannot strictly be excluded.

Adenocarcinoma↗

Dose-response to acellular pertussis vaccine and comparison with whole cell pertussis vaccine at 15-24 months and 4-6 years of age. Acellular Pertussis Vaccine Study Team.

In a randomized double-blind trial 55 children of 15-24 months and 56 children of 4-6 years of age previously immunized with whole-cell DTP (WC-DTP) received acellular pertussis DTP vaccines containing 12.5 micrograms (AC-12.5) or 25 micrograms (AC-25) each of pertussis toxoid (PT) and filamentous haemagglutinin (FHA) per dose of WC-DTP. No differences in antibody responses or adverse events were noted for children who received AC-25 as compared with AC-12.5. All three groups had significant increases in pertussis agglutinins, but the geometric mean titre (GMT) for 4-6-year-old children who received WC-DTP was higher than the GMT for children who received acellular vaccine. No significant differences were noted in the GMT of antibodies to FHA or PT between children who received WC-DTP and recipients of acellular vaccine. The rates of several adverse reactions were significantly (p less than or equal to 0.05) higher for recipients of WC-DTP, and children given WC-DTP were significantly (p less than or equal to 0.00001) more likely to have received acetaminophen. These acellular vaccines are safe and as immunogenic for FHA and PT as WC-DTP when administered as the fourth or fifth dose to children who received three doses of WC-DTP in infancy. The lower (12.5 micrograms) dose of acellular vaccine was as effective as the higher (25 micrograms) dose in inducing antibodies to FHA and PT in children 15-24 months and 4-6 years of age.

Antibodies↗

Evaluation of a live attenuated, cold-adapted parainfluenza virus type 3 vaccine in children.

Cold passage 18 (CP18) parainfluenza virus type 3 (PIV-3) vaccine was evaluated in a double-blind, randomized, placebo-controlled study of 95 infants and young children. None of 19 seropositive older children 41 to 124 months old became infected when 10(6) 50% tissue culture infective doses (TCID50) of vaccine virus was administered intranasally. Two of nine and seven of twenty-four young seropositive children given 10(5) or 10(6) TCID50 of CP18 PIV-3, respectively, became infected. Each of four seronegative young children became infected, as indicated by virus shedding and antibody response, when given 10(6) TCID50 of CP18 PIV-3 intranasally. Illness was not observed in seropositive children. Two of the four seronegative children developed a mild illness characterized by rhinorrhea and wheezing on auscultation; none had fever. In one case, vaccine virus spread from a vaccine to a sibling control but did not cause illness. The vaccine is attenuated relative to wild-type PIV-3, but additional attenuation will be required to achieve a satisfactory PIV-3 vaccine.

Adaptation, Physiological↗

Basal cells of H-Dunning tumor are myoepithelial cells. A comparative immunohistochemical and ultrastructural study with male accessory sex glands and mammary gland.

Recent immunohistochemical studies have shown that basal cells in human prostatic epithelium are not myoepithelial cells. Since in the literature the Dunning tumor, originally described as a rat prostate carcinoma derived from the dorsolateral prostate of a Copenhagen rat, was reported to have myoepithelial cells, a comparative immunohistochemical and ultrastructural study was performed in the H-, HIF- and AT3-lines of the Dunning tumor, the male accessory sex glands (ventral, dorsal, lateral prostate, coagulating gland, bulbourethral gland) and the mammary gland of both Copenhagen and Wistar rats. Mono- and polyclonal antibodies directed against intermediate filament proteins (cytokeratin, desmin, vimentin) and the contractile proteins (alpha-actin, muscle type specific myosin, tropomyosin) were used along with phalloidin decoration of F-actin. As in the human prostate, none of the rat prostate lobes in either strains did contain basal cells expressing cytokeratin along with alpha-actin, myosin and tropomyosin Cells representing fully differentiated myoepithelial cells, however, were present as anticipated in the mammary gland, the bulbourethral gland and the H-tumor line of the Dunning tumor. This finding is difficult to reconcile with the contention of a prostatic origin of the H-Dunning tumor. Further studies are required to classify the epithelial parental tissue in order to define the true origin of the H-Dunning tumor and the tumor lines derived thereof.

Actin Cytoskeleton↗

Safety and immunogenicity of human rotavirus vaccine strain M37 in adults, children, and infants.

Rotavirus vaccine strain M37 (serotype 1), recovered from the stool of an asymptomatic newborn infant and serially passaged in cell culture, was given orally to adults, children, and infants. Serologic responses were detected by neutralization assay or EIA in 59% of 17 adults (10(5)-pfu dose), 55%-60% of 21 infants and children (10(4)-pfu dose), and 70% of 10 infants (10(5)-pfu dose), vaccine virus was shed by 24%, 20%-36%, and 70%, respectively. In adults, neutralizing antibody rises to strain M37 and the related serotype 1 strain Wa occurred with equal frequency (41% vs. 47%). In pediatric subjects, the former were more frequent (36%-40%) than the latter (10%-18%). This was also true of 8 infants who received two doses of vaccine. Mild gastrointestinal illnesses occurred with equal frequency in pediatric subjects who received vaccine or placebo. Thus, strain M37 was well tolerated and immunogenic in young infants, but elicited primarily vaccine-strain-specific rather than serotype-specific neutralizing antibody responses.

Adult↗

[Asymptomatic calcified aneurysm of the inferior pancreaticoduodenal artery--differential diagnostic considerations].

A calcified aneurysm of the inferior pancreaticoduodenal artery with simultaneous occlusion of the celiac axis but without any local symptoms is presented. In the description of the diagnostic procedure, the considerations relating to differential diagnosis against solitary circumferentially calcified masses in the right upper quadrant of the abdomen are discussed. As a result of increasingly sophisticated examination techniques, especially digital subtraction angiography, computed tomography and ultrasonography, these aneurysms, which were formerly thought to be rare, are now discovered surprisingly often. Knowledge of this vascular malformation and its differential diagnoses helps to avoid risky methods of examination.

Aneurysm↗

Human-rhesus reassortant rotavirus vaccines: safety and immunogenicity in adults, infants, and children.

Human-rhesus reassortant rotavirus vaccines derived from rhesus rotavirus and human rotavirus serotypes 1, 2, or 4 were administered to adults, children, and infants after they had been given sodium bicarbonate buffer. Over 70% of infants and children developed antibody responses to or shed the candidate vaccine viruses. Individuals with prevaccination serum neutralization antibody titers less than or equal to 1:160 had significantly (P less than .0001) higher response rates than did individuals with prevaccination titers greater than or equal to 1:320. Similarly, shedding of vaccine viruses occurred significantly (P = .03) more often in children than adults and was inversely correlated with prevaccination antibody titers. No illnesses were observed in adults, and the vaccines were well tolerated in children. An increased rate of low-grade, transient fever (38.0-38.8 C) was noted only in children given serotype 2 vaccine, compared with controls (P = .006). No significant differences in the average number of unformed stools passed during the seven days after vaccination were noted in vaccinees versus controls. These vaccine strains are currently undergoing further evaluation in expanded clinical trials.

Adult↗