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H Sariola

Publications and source records attributed to H Sariola.

At least 73 records · Page 4Linked to original sources
PubMed1994

Integrins and laminins in human renal carcinoma cells and tumors grown in nude mice.

We studied by indirect immunofluorescence microscopy the distribution of integrins and laminins in four human renal cell carcinoma cell lines (CAKI-2, A498, CAKI-1, and ACHN) in vitro and in s.c. xenografts in nude mice. In vitro, all four cell lines expressed the alpha 1, alpha 3, alpha v, beta 1, beta 3, and beta 5 subunits and three expressed the alpha 6 subunit; all cell lines expressed laminin A, B1, and B2 chains. Histologically, the CAKI-2 and A498 cells formed differentiated grade 1 (G1) and G2 tumors, respectively, while the CAKI-1 and ACHN cells formed poorly differentiated G3 tumors. The described integrin profile was largely retained upon xenografting. Basal polarization of the alpha 3 and alpha 6 integrin subunits was found in the differentiated tumors, and human laminins were detected as discrete linear structures surrounding tumor cell clusters in these tumors, suggesting that the cells have retained a polarized cell-laminin interaction characteristic of normal tubular epithelial cells. A disorganized distribution of integrins and laminins was noted in the G3 tumors. We conclude that these renal carcinoma cell lines displayed an integrin repertoire similar to that of clinical renal carcinomas and retained it upon xenografting. Furthermore, the organization of integrins and laminins in the xenografts correlated with histological grade.

Animals↗
PubMed1994

Antisense inhibition of low-affinity nerve growth factor receptor in kidney cultures: power and pitfalls.

1. Antisense inhibition of gene expression implies that the expression of the target protein is selectively inhibited at either the translational or the transcriptional level by complementary DNA or RNA constructs that are antiparallel to the target sequence. The antisense inhibition strategy provides means to study the roles of individual proteins and has, in spite of its limitations, gained a wide range of both therapeutic and experimental applications. 2. In developmental biology, protein expression has been selectively inhibited by the use of antisense gene transfection and by antisense deoxyoligonucleotides. The transfectability of embryonic tissues is variable, but in general fetal and embryonic cells take up foreign DNA relatively efficiently, in particular, short deoxyoligonucleotides that penetrate mesenchymal cells within a few hours without any manipulation. 3. We have now evaluated the advantages and pitfalls of antisense inhibition by deoxyoligonucleotides in organ culture and describe our experience from the inhibition of low-affinity nerve growth factor receptor expression in embryonic mouse and rat kidneys. 4. The expression of nerve growth factor receptor can be specifically inhibited by deoxyoligonucleotides, but the target sequence-dependent window of, in particular, phosphorothioate-modified oligonucleotides is quite narrow. The culture conditions affect the response to the oligonucleotides and their cellular incorporation is variable with respect to the cell type and stage of differentiation.

Animals↗
PubMed1994

Does disordered upper gastrointestinal motility predispose to Helicobacter pylori colonization of the stomach in children?

Helicobacter pylori is an important factor in the pathogenesis of chronic gastritis and gastroduodenal ulcer disease. However, the basic causal mechanisms of H pylori colonization on the gastric mucosa are still unclear. The authors evaluated the prevalence of H pylori colonization in 266 children who underwent upper gastrointestinal endoscopy during a 12-month period. The indications for endoscopy were follow-up of esophagitis related to gastroesophageal reflux (n = 17), suspicion of gastroesophageal reflux (n = 51), abdominal pain (n = 28), vomiting (n = 30), follow-up of esophageal atresia (n = 46) and duodenal atresia (n = 28), inflammatory bowel disease (n = 28), and miscellaneous (n = 38). The methods used to detect H pylori colonization were histology and the rapid urease test. H pylori colonization was demonstrated in 31 (11.6%) of the 266 patients. In two patient groups, a high prevalence of colonization was identified. In patients with an operated duodenal atresia, 36% (10 of 28) had H pylori on the gastric mucosa. The organism was demonstrated on the gastric mucosa in 47% (8 of 17) of the patients with gastroesophageal reflux-related esophagitis; five of the eight patients had neurological impairment. In the other patient groups, the prevalence of H pylori infection ranged from 2% to 14%. The present study suggests that, in children, the disturbed esophagogastroduodenal motility, which is commonly associated with gastroesophageal reflux and duodenal atresia, predisposes to H pylori infection.

Adolescent↗
PubMed1994

The prevalence of child sexual abuse in Finland.

The prevalence and context of child sexual abuse was surveyed in Finland. A random sample of 409 comprehensive school classes with about 9,000 15-year-olds were asked to anonymously fill out questionnaires. The majority (93%) filled the questionnaires out in the privacy of the school nurse's office, the rest in their classrooms. Eighty-nine percent of the selected classes participated in the survey and the response rate of the students in those classes was 96%. Eighteen percent of girls and 7% of boys reported sexual experiences with a person at least 5 years older than themselves at the time of the incident. Voluntary experiences with boy or girlfriends were then excluded to get an estimate of the prevalence of sexual abuse. About 6-8% of girls and 1-3% (depending on the used criteria) of boys reported experiences that could be classified as sexual abuse. Force had been used against 2% and violence against 1% of the girls. Regional differences were so great both in sexual experience and in sexual abuse that they could be interpreted as giving support to a "subculture theory" of sorts. The results are compared with prevalence estimates from the United States and the Nordic countries.

Adolescent↗
PubMed1994

Human laminin M chain (merosin): complete primary structure, chromosomal assignment, and expression of the M and A chain in human fetal tissues.

The primary structure of the human laminin M chain was determined from cDNA clones isolated from human placental libraries. The clones covered a total of 6,942 bp, with 49-bp encoding a 5' end untranslated region and 6,893-bp coding for a translated sequence. The complete human laminin M chain contains a 22-residue signal peptide and 3,088 residues of the mature M chain. The M chain has a domain structure similar to that of the human and mouse A chains. The homology between the two human laminin heavy chains is highest in the short arm region and lowest in the long arm helical domain I + II. Northern blot analysis of human fetal tissues showed that the M chain was expressed in most tissues such as cardiac muscle, pancreas, lung, spleen, kidney, adrenal gland, skin, testis, meninges, choroid plexus, and some other regions of the brain, but not in liver, thymus, and bone. In situ hybridization localized the expression of the M chain gene to cells of mesenchymal origin. In contrast, expression of the A chain was observed only in kidney, testis, neuroretina and some region of brain as determined by Northern analyses. Epithelial and endothelial cells were negative for both M and A chain gene transcripts. The gene for the human M chain (LAMM) was localized to chromosome 6q22-->23.

Amino Acid Sequence↗
PubMed1994

The effect of plain 0.5% 2-chloroprocaine on venous endothelium after intravenous regional anaesthesia in the rabbit.

The possible venous endothelial toxicity of 0.5% 2-chloroprocaine without additives in intravenous regional anaesthesia (IVRA) was evaluated in rabbits. After exsanguination of a hind limb with an Esmarch's bandage a neonatal blood pressure cuff around the thigh was inflated (250 mmHg). For IVRA 4 ml of either plain 0.5% 2-chloroprocaine (pH 3.7), 0.9% NaCl (pH 6.0) or acidified NaCl (pH 3.7) was injected i.v. to the exsanguinated limb in a randomized, double-blind fashion. Each group comprised 15 rabbits. Eleven rabbits received 4 ml of 0.5 M or 1.0 M KCl, for the production of positive controls. Two hours after injection of the test solution the tourniquet was deflated and venous biopsies were taken one and 24 hours later for histological and immunocytochemical examination. Five to eight 24-hour samples from each group were also processed for electron microscopy. A macroscopic thrombus formation was observed in four rabbits after KCl and in two after acidified NaCl administration. No inflammatory changes were observed at histologic and immunocytochemical examination of any of the vein samples. Electron microscopy revealed that KCl had caused severe damage to the venous endothelium of four out of five samples and acidified NaCl had caused moderate damage to the endothelium of two out of seven samples. 2-chloroprocaine had caused moderate damage in four and severe damage in two of the vein samples; two samples were normal. No thrombus formation occurred. It is concluded that additive-free 2-chloroprocaine caused damage to the venous endothelium in rabbits when used for IVRA.

Anesthesia, Conduction↗
PubMed1994

Pathology of renal arteries of dyslipidemic children with congenital nephrosis.

Congenital nephrotic syndrome of the Finnish type (CNF) is well characterized in infants and associated with major lipid risk factors for atherosclerosis. This study was undertaken to investigate if any arterial pathology is present in children with CNF and, if so, to describe its nature in renal arteries collected at nephrectomy at a mean age of 12.5 +/- 4.4 months. Denuded endothelial injury and intimal thickening were seen in 9 out of 10 patient specimens of renal arteries. Intimal thickening contained loose abundant extracellular matrix with a few smooth muscle or myofibroblastoid cells. Only a few Sudan black- or oil red O-positive lipid droplets were found in six and seven samples, respectively. Areas immunoreactive with antibodies against apoprotein B were seen in only two specimens. Immunohistochemistry did not reveal any activated T or B cells, or any expression of IL-1 or IL-2 receptors. Macrophages were present in only two specimens. No foam cells were seen. We conclude that the vascular pathology together with altered lipoprotein metabolism indicates that children with CNF might be at risk for early atherosclerotic arterial disease, particularly if their hyperlipidemia persists.

Apolipoproteins B↗
PubMed1994

Neurotrophins and ciliary neurotrophic factor: their biology and pathology.

Neurotrophins (NTFs) and ciliary neurotrophic factor (CNTF) induce the differentiation of neuronal cells, rescue them from naturally occurring death, and trigger neuronal regeneration. The NTFs bind to two classes of cell surface receptors, whereas CNTF receptor is composed of three subunits. The functions of these polypeptide survival factors with trophic action on nerve cells have recently been approached by the targeted disruption of the CNTF, NTF and their receptor genes by the homologous recombination technique. The embryonic growth and morphogenesis of these gene 'knock-out' mice is normal, but they develop with defects in various subsets of the peripheral nervous system, and the homozygous mutant mice often die during the early postnatal period. Disturbances in the biology of NTFs and CNTF have recently been implicated in the pathogenesis of certain common neurodegenerative disorders, such as Parkinson's disease, motor neurone diseases, and Alzheimer's disease. Intensive research on their pharmaceutical perspective has, therefore, been provoked. All neurotrophins and CNTF can now be synthesized on a large scale as biologically active recombinant proteins, and several alternatives for their local applications to the target tissue have been presented. Their therapeutic potential is discussed.

Animals↗
PubMed1994

Neuronal characteristics in embryonic renal stroma.

The metanephric mesenchyme is considered a homogeneous population of predetermined, but pluripotent cells with a nephrogenic bias. By an inductive stimulus, the mesenchyme is programmed to differentiate into the various epithelial phenotypes of the secretory nephron. A fraction of the mesenchymal cells, however, remains in the interstitium between the nephrons and differentiates into spindle-shaped, clear-cytoplasmic renal stroma. We have analyzed the molecular nature of these cells in order to discover the specific cell types that could be involved in the morphogenetic processes during kidney differentiation. In situ hybridization reveals neurofilament light protein mRNA, and immunohistology shows neurofilament light and medium proteins in the stromal cells around kidney tubules. By immunohistochemistry these peritubular stromal cells can be distinguished from the neuronal cells of the renal microganglion: the peritubular stromal cells are neurofilament-positive but L1 neural cell adhesion protein-negative, whereas the neuronal cells with axonal extension are both neurofilament-positive and L1 neural cell adhesion protein-positive. Proliferation index of the stromal cells was low as compared to tubular cells, as shown by bromodeoxyuridine incorporation.

Animals↗
PubMed1993

WT-1 is required for early kidney development.

In humans, germline mutations of the WT-1 tumor suppressor gene are associated with both Wilms' tumors and urogenital malformations. To develop a model system for the molecular analysis of urogenital development, we introduced a mutation into the murine WT-1 tumor suppressor gene by gene targeting in embryonic stem cells. The mutation resulted in embryonic lethality in homozygotes, and examination of mutant embryos revealed a failure of kidney and gonad development. Specifically, at day 11 of gestation, the cells of the metanephric blastema underwent apoptosis, the ureteric bud failed to grow out from the Wolffian duct, and the inductive events that lead to formation of the metanephric kidney did not occur. In addition, the mutation caused abnormal development of the mesothelium, heart, and lungs. Our results establish a crucial role for WT-1 in early urogenital development.

Alkaline Phosphatase↗
PubMed1993

Surgical treatment of intractable cholestasis associated with total parenteral nutrition in premature infants.

We report surgical reversal of intractable total parenteral nutrition (TPN)-associated cholestasis refractory to conservative treatment in 9 premature infants. Indications for TPN were poorly tolerated enteral feedings in all patients. Five patients had undergone gastrointestinal operations; in addition, 7 of the 9 patients had had bacterial sepsis. The median duration of TPN was 28 days (range, 20 to 50 days). The median duration of preoperative full enteral nutrition after weaning from TPN was 34 days (range, 16 to 95 days). All patients had progressive conjugated hyperbilirubinemia, no excretion of Tc-labeled HIDA to the biliary tree and duodenum, and markedly elevated liver enzyme values. Intraoperative cholangiography showed normal biliary anatomy in all cases; in addition, 2 patients had gallbladder stones. Bile was hyperviscous in all patients and contained biliary sludge in 4. The biliary tree was irrigated and the liver biopsied in all patients. The gallbladder was removed from 2 patients who had stones in the gallbladder. Liver histology was consistent with TPN-associated cholestasis in all cases, and in addition, 4 cases showed significant destruction of intrahepatic bile ducts. One patient died 2 weeks postoperatively from intracerebral hemorrhage. Jaundice completely resolved in other patients within 2 weeks. HIDA-biligraphy performed 1 to 2 months postoperatively showed normal excretion of the radioactive marker to the biliary tree and duodenum in all cases. The functional abnormality in bile excretion and bile duct motility in TPN-associated cholestasis may be reversed by irrigation of the biliary tree. Surgical intervention should be considered when cholestasis is progressive and refractory to medical management.

Cholestasis↗
PubMed1993

Chronic esophagitis and gastric metaplasia are frequent late complications of esophageal atresia.

Long-term follow-up examination with esophagogastroduodenoscopy was performed on 39 esophageal atresia patients 2 to 11 years (mean, 7.6) after the anastomotic operation. Nine of these patients had undergone fundoplication for symptomatic gastroesophageal reflux. The subjective results at the last follow-up were as follows: excellent in 25, good in 10, and fair in 4 patients. The endoscopic findings were normal in 17 patients. Endoscopy of the remaining 22 patients showed esophagitis in 20, 5 associated with Barrett's change. Hiatal hernia was found in 10 patients. The fundoplication was totally or partially disrupted in 3 patients. Esophageal biopsies were obtained from 37 patients. The histological findings were as follows: esophagitis in 21, gastric metaplasia in 3, and normal esophageal mucosa in 13 patients. The endoscopic and histological findings correlated poorly with subjective results as more than half of the patients with excellent subjective results had esophagitis, one of them with gastric metaplasia. Therefore, long-term endoscopic follow-up of all esophageal atresia patients is warranted.

Child↗
PubMed1993

Constipation is a major functional complication after internal sphincter-saving posterior sagittal anorectoplasty for high and intermediate anorectal malformations.

Anorectal function was clinically, manometrically, and radiologically followed-up in 40 patients who underwent an internal sphincter-saving posterior sagittal anorectoplasty in 1984 to 1989. The functioning internal sphincter was manometrically verified in 83% (33/40) of the patients. Soiling related to sphincter insufficiency was found in only 4 of the 33 patients with a functioning internal sphincter; 5 of the 7 patients without an internal sphincter had soiling. Symptomatic constipation was found in 73% (24/33) of the patients with a functioning internal sphincter, but in only 28% (2/7) of the patients without this structure. Constipation was not associated with a stenotic anal outlet in any patient. On anorectal manometry, there was no statistical difference in basal and pressures and internal sphincter reflex threshold values between constipated and nonconstipated patients. Histologically, ganglion cells were found in the proximal anal canal in all cases. The radiological size of the rectal pouch before closure of the protecting colostomy had a positive correlation with the severity of constipation. Medical treatment with diet and bulk-laxatives (13 patients) or with stimulant laxatives and occasional enemas (11 patients) successfully relieved constipation in 24 patients. In 2 patients, the symptoms were refractory to medical treatment and a resection of the megarectum was required. In conclusion, the preservation of the internal sphincter in patients with high or intermediate anorectal anomalies gives a good fecal continence outcome, but is associated with a high incidence of symptomatic constipation.

Anal Canal↗