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Biomedical subjects

B Sandstedt

Publications and source records attributed to B Sandstedt.

At least 73 records · Page 4Linked to original sources
PubMed1995

Association of neurotrophin receptor expression and differentiation in human neuroblastoma.

Interactions of the trk family of tyrosine kinase receptors with neurotrophins result in growth and maturational changes in neuronal cells. The continued progression, maturation, or regression of neuroblastoma, an embryonal, sympathetic nervous system-derived tumor of infants and children, might be governed by neurotrophic influences. Immunocytochemistry was utilized to evaluate TrkA, TrkB, and TrkC protein expression at the cellular level in the developing human fetal sympathetic nervous system and in a selection of neuroblastoma tumor specimens. TrkA and TrkC expression was identified in sympathetic ganglia and within the adrenal medulla, with intense TrkB expression restricted to paraganglia, of the normal developing human sympathetic nervous system. In neuroblastoma, pp140trkA expression correlated positively with favorable tumor stage (P = 0.0027) and favorable outcome (P = 0.026). No statistically significant correlation of TrkC expression with outcome was evident; however, both TrkA and TrkC expression was most apparent in tumor cells of increased differentiation. TrkB expression was primarily localized to cells within the fibrovascular tumor stroma. A model of neurotrophin receptor expression and neurotrophin reactivity with differentiation is proposed. The existence and spatial distribution of neurotrophin receptors in neuroblastoma lend supportive evidence that neurotrophic influences may be involved in tumor persistence or regression.

Adrenal Medulla↗
PubMed1995

IGF2 expression is a marker for paraganglionic/SIF cell differentiation in neuroblastoma.

Neuroblastoma is a childhood tumor of the sympathetic nervous system. Observations in the Beckwith-Wiedemann syndrome suggest that sympathetic embryonal cells with an abundant expression of the insulin-like growth factor 2 gene (IGF2) may be involved in the genesis of low-malignant infant neuroblastomas. We have therefore compared the cell type-specific IGF2 expression of the human sympathetic nervous system during early development with that of neuroblastoma. An abundant expression in normal sympathetic tissue was specific to extra-adrenal chromaffin cells, ie, paraganglia and small intensely fluorescent (SIF) cells, whereas sympathetic neuronal cells were IGF2-negative. A subpopulation of neuroblastomas expressed IGF2, which correlated with an early age at diagnosis, an extra-adrenal tumor origin, and severe hemodynamic signs of catecholamine secretion. Histologically IGF2-expressing tumors displayed a lobular growth pattern, and expression was restricted to the most mature and least proliferative cells. Typically, these cells were morphologically and histochemically similar to paraganglia/SIF cells and formed distinct ring-like zones in the center of the lobules around a core of apoptosis-like tumor cells. The similarities found between IGF2-expressing neuroblastoma cells and paraganglia/SIF cells in terms of histological features, anatomical origin, and age-dependent growth suggest a paraganglionic/SIF cell lineage of most infant tumors and also of extra-adrenal tumors diagnosed after infancy. Furthermore, since paraganglia/SIF cells undergo postnatal involution, the same cellular mechanism may be responsible for spontaneous regression in infant neuroblastoma.

Biomarkers, Tumor↗
PubMed1995

Decreased expression of Ras GTPase activating protein in human trophoblastic tumors.

The normally developing placenta undergoes extensive but regulated noninvasive cellular proliferation. Various proto-oncogenes and growth factors have been associated with the regulation of trophoblastic placental growth. Activation of some oncogenes and altered expression of growth factors have been demonstrated in trophoblastic tumors (hydatidiform mole and choriocarcinoma). The ras proto-oncogene plays a key role in the signal transduction cascade of activated growth factors, and is known to be activated or overexpressed in multiple tumor types. Ras GTPase activating protein (RasGAP), a major down-regulator of ras activity, is present at high levels in placenta. To assess the role that Ras-GAP plays in the development of trophoblastic tumors, we performed immunohistochemical analyses with anti RasGAP antibodies of normal placentas, hydatidiform moles, invasive moles, and malignant choriocarcinomas. Normal placentas and noninvasive hydatidiform mole displayed intense positive staining confined to trophoblasts, whereas no staining was observed in the trophoblasts of invasive moles or choriocarcinomas. Thus, there was an inverse correlation between expression levels of RasGAP protein and the invasive potential and malignant phenotype in human trophoblastic tumors. The data indicate that RasGAP may play a regulatory role in trophoblast proliferation and that abolishing its activity may be associated with malignant transformation of these cells.

Cell Transformation, Neoplastic↗
PubMed1994

A prospective study of first attacks of inflammatory bowel disease and infectious colitis. Clinical findings and early diagnosis.

In 105 patients with a first attack of colitis, clinical, microbiologic, laboratory, and histologic features were studied prospectively with the aim of differentiating inflammatory bowel disease (IBD) from infectious colitis as early as possible. Of the patients who proved to have IBD the mode of onset of diarrhoeal symptoms was insidious in 56% and non-insidious in 44%, whereas in 81% of those who proved to have infectious colitis the onset was acute. Most patients with infectious colitis presented within 1 week, had early fever, and did not show histologic features characteristic of IBD. Most IBD patients with a more acute onset had clinical warning signs of IBD such as slight previous bowel symptoms, a late presentation time (> 1 week), and absence of early fever or had histologic features characteristic of IBD. These features were basal plasmacytosis, crypt distortion, more than two vertical crypt branches, villous mucosa, mucosal atrophy, epithelioid granuloma, and Paneth cell metaplasia. Moreover, 61% of the IBD patients with a non-insidious onset fell ill in connection with travelling abroad, gastrointestinal infection, or treatment with antibiotics. Knowledge of the above clinical and histologic factors will facilitate differentiation of IBD from infectious-type colitis.

Adolescent↗
PubMed1994

A prospective study of first attacks of inflammatory bowel disease and infectious colitis. Histologic course during the 1st year after presentation.

To investigate the possibilities of differentiating between inflammatory bowel disease (IBD) and infectious colitis on histologic grounds, a prospective histologic study of 105 patients with a first attack of colitis was undertaken. Rectal biopsies were performed on four occasions during 1 year. The strongest predictor of IBD was basal plasmacytosis, followed by more than two vertical crypt branches per medium-power field, crypt distortion, villous mucosa, and mucosal atrophy. These signs were rarely found among patients with infectious colitis. Their frequency increased with the interval between initial symptoms and the first biopsy. To study the development of histologic features in the absence of treatment, the IBD patients were divided into groups depending on this interval. Focal or diffuse basal plasmacytosis increased from 38% in the group with an interval of 1-15 days to 89% in those who presented in 121-300 days, and crypt distortion from 0% to 78%, whereas absence of signs indicating IBD decreased from 62% to 11%. The presence of focal basal plasmacytosis seems to be the earliest sign of IBD. The frequency of histologic signs indicating IBD was maximal (88%) at the 1-week biopsy. After recovery, the basal plasmacytosis and villous mucosa decreased, whereas crypt distortion and mucosal atrophy remained unchanged. Early treatment did not prevent the appearance of any feature.

Adult↗
PubMed1994

The cell type-specific IGF2 expression during early human development correlates to the pattern of overgrowth and neoplasia in the Beckwith-Wiedemann syndrome.

Overstimulation by insulin-like growth factor II is implied in several overgrowth conditions and childhood cancers. We have therefore studied spatial and temporal expression patterns of the insulin-like growth factor II gene (IGF2) and the insulin-like growth factor type 1 receptor gene during normal human development (5.5 to 23.0 weeks postfertilization). The set of cell types with the most abundant IGF2 expression correlated strikingly to the organomegaly and tumor predisposition of the Beckwith-Wiedemann syndrome. Intrauterine growth and postnatal organ weights of a prematurely born child with a full-blown syndrome are presented. The cell type-specific IGF2 expression of these organs and of multifocal Wilms' tumors from two other children affected by the Beckwith-Wiedemann syndrome were also studied. The results clarify and extend previous findings concerning human prenatal IGF2 expression and are consistent with a short range overstimulatory role of locally produced IGF II ensuing after the first trimester in the Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann Syndrome↗
PubMed1993

Helicobacter pylori infection, ABO blood group, and effect of misoprostol on gastroduodenal mucosa in NSAID-treated patients with rheumatoid arthritis.

Our aim was to investigate the effect of misoprostol on NSAID-induced gastroduodenal mucosal damage in patients with rheumatoid arthritis. The study included 40 patients, and it was designed as a double-blind, placebo-controlled trial. Misoprostol significantly reduced the gastroduodenal mucosal lesions found at endoscopy (P < 0.05) and prevented the development of ulcers. The cumulative incidence of ulcers at four weeks was 5% in the placebo group and 0% in the misoprostol group. The basal and pentagastrin-stimulated acid output as evaluated after 23 days of treatment with misoprostol was not significantly affected. Forty-one percent of the patients had signs of current Helicobacter pylori infection, 33% had positive serology only, and 26% had no evidence of infection. Most of the patients with current infection belonged to blood group O (P < 0.05). Misoprostol treatment did not affect the occurrence of Helicobacter pylori or the rheumatic disease activity. It is concluded that the protective actions of misoprostol on the gastroduodenal mucosa of NSAID-treated patients are largely mediated by mechanisms other than inhibition of acid secretion. The relationship among active Helicobacter pylori infection, blood group O, and peptic ulcer may be helpful to identify a subpopulation of patients taking NSAIDs at risk of developing peptic ulcers.

ABO Blood-Group System↗
PubMed1993

A prospective study of first attacks of inflammatory bowel disease and non-relapsing colitis. Microbiologic findings.

In 105 patients with a first attack of colitis, thorough microbiologic investigations of rectal biopsy, faecal, and serum samples were performed with the aims of identifying the colitis-causing agents and shedding light on factors that may precipitate or aggravate the onset of inflammatory bowel disease. Sixty-one patients were found to have inflammatory bowel disease. In 13 (21%) of these patients microbial findings were positive. Eight of the 61 patients fell ill during or immediately after antibiotic treatment, and 10 while travelling abroad. Forty-one of the 105 patients had non-relapsing colitis. In 32 (78%) of these the microbial findings were positive. Six of these 41 patients fell ill during or immediately after antibiotic treatment, and 14 while travelling abroad. Alteration of the intestinal microflora on travelling, gastrointestinal infection, or treatment with antibiotics seems to precipitate or aggravate the symptoms in latent inflammatory bowel disease. In such patients the mode of onset is often changed from insidious to more acute, which may cause difficulty in differentiation from non-relapsing colitis.

Acute Disease↗
PubMed1991

Placental morphology in relation to umbilical artery blood velocity waveforms.

The association between umbilical artery flow velocity waveforms, placental morphology and arterial vascular pattern was investigated in 30 pregnant women at risk for intra-uterine growth retardation. The blood velocity waveform was assessed in the umbilical arteries with pulsed Doppler ultrasound. Placentas from fetuses with an end-diastolic zero flow were small and thick with an extrachorial configuration, marginal cord insertion, magistral or mixed allantochorial vessel pattern and few cotyledons. The incidence and the extension of gross lesions were slightly increased in these placentas compared to placentas from fetuses with a normal S/D ratio (peak systolic velocity/minimum diastolic velocity). Placentas from fetuses with an increased S/D ratio (greater than +2SD) were large and thin with a high maximum diameter/maximum thickness ratio. Heavily smoking mothers were overrepresented in the group, with an increased S/D ratio and corresponding SGA infants. End-diastolic zero flow in the umbilical artery was strongly correlated with placental developmental abnormalities.

Angiography↗
PubMed1991

Grading of human urothelial carcinoma based on nuclear atypia and mitotic frequency. I. Histological description.

The World Health Organization (WHO) grade II bladder tumors constitute a clinically and histologically heterogeneous group due to imprecise histological definitions. In an attempt to improve this problem 124 transitional cell carcinomas of the bladder were histologically reviewed using a modified Bergkvist system. The grade II tumors were divided into 2 groups, grades IIa and IIb, mainly with reference to the degree of nuclear atypia and number of mitoses. Using definitions possible to express by numerical means, the separation was easy and reproducible. Due to great histological resemblance between certain close grades we propose a new grading system with 3 grades combining I and IIa (grade A), IIb and III (grade B), and a third group (grade C) for the anaplastic tumors.

Carcinoma, Transitional Cell↗
PubMed1991

Grading of human urothelial carcinoma based on nuclear atypia and mitotic frequency. II. Prognostic importance.

A grading system was applied in a retrospective study of 124 patients with transitional cell carcinoma of the bladder using a modified Bergkvist system. The intermediate World Health Organization (WHO) grade II tumors were divided into supposedly benign and malignant forms of grades IIa and IIb, respectively. The 5-year survival was 92% for patients with grade IIa urothelial carcinoma, compared to 43% for patients with grade IIb tumors. The corresponding figures for grades I and III tumors were 100 and 44%, respectively. When excluding carcinoma in situ (5-year survival 50%) no patient with a noninvasive tumor (stage Ta) died of bladder carcinoma within 5 years, compared to 50% of those with invasive cancers (stages T1 to T4). We propose a new grading system in which grades I and IIa are embraced as grade A, grades IIb and III as grade B, and grade IV as grade C. The 5-year survival rate in the 3 grades was 94, 44 and 27%, respectively. Grade A seems to represent a type of tumor with universally favorable prognosis, in contrast to grades B and C. This offers practical advantages, since the former can be treated conservatively, whereas the latter need more urgent radical intervention, especially in patients in whom invasive growth is recorded.

Carcinoma, Transitional Cell↗
PubMed1991

Clinical and histologic features differentiating non-relapsing colitis from first attacks of inflammatory bowel disease.

This is a study of first attacks of colitis, evaluating prospectively the overall course with repeated histologic, clinical, laboratory, and initial microbiologic examinations. Forty-two attacks of colitis could after a follow-up period of 5.5 years be separated into relapsing and non-relapsing types. Relapse was chosen as a prerequisite for a final diagnosis of inflammatory bowel disease. In the non-relapsing group 72% of the patients harboured enteropathogenic bacteria. An insidious onset of diarrhoeal symptoms was highly discriminant of inflammatory bowel disease, whereas an acute onset mostly occurred in patients with non-relapsing colitis. Macroscopic differentiation at sigmoidoscopy was not possible. Distorted crypt architecture (92%) and/or basal plasmacytosis (77%) at initial biopsies strongly indicated inflammatory bowel disease but was also found transiently in patients with infectious colitis (19%). Thus, careful microbiologic and clinical investigation and repeated histologic examinations are necessary to distinguish infectious colitis from inflammatory bowel disease.

Adult↗
PubMed1991

Effects on chest pain of early thrombolytic treatment in suspected acute myocardial infarction: results from the TEAHAT Study.

In a randomized, double-blind study, in which recombinant tissue plasminogen activator (rt-PA) administered at an early stage was compared with placebo in patients with suspected acute myocardial infarction (AMI), the effects on pain were studied in 312 patients. Inclusion criteria were as follows: (a) chest pain of duration less than 2 h and 45 min; and (b) age less than 75 years. Chest pain was estimated subjectively by the patients, using a 10-point numerical rating scale, at hourly intervals for the first 24 h, and by the requirement for narcotic analgesics. Compared with placebo, rt-PA treatment resulted in a 43% reduction in mean total pain score (P less than 0.0001), a 26% reduction in pain duration (P less than 0.01), and a 33% reduction in morphine requirement (P = 0.01). Fifty-seven per cent of all patients developed a confirmed AMI. In these subjects rt-PA reduced the pain score by 46% (P less than 0.001). Among patients without confirmed AMI, a 37% reduction in pain score was observed (P = 0.05). The effect on pain was most marked in patients with ST-elevation on the initial ECG. We conclude that early treatment with rt-PA in suspected AMI reduces chest pain considerably. The effect is most marked in patients with ST-elevation on the initial ECG.

Aged↗