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Effects of pre-weaning undernutrition and post-weaning rehabilitation on polyphosphoinositide pools in rat brain regions.

In order to assess the effects of undernutrition during the pre-weaning period on polyphosphoinositide (PolyPI) pools in rat cerebral cortex, brain stem, and cerebellum, dams were fed 5% (L-) or 22% (L+) protein diets from birth to weaning and the pups were used at this age for analyses. To examine rehabilitation post-weaning, L- and L+ pups were fed 22% protein diets (P+) for an additional six week period. Rats were decapitated and the dissection begun either immediately ("0 min" samples) or 10 min later (10 min samples). Body and tissue weights, and cerebroside levels were determined in addition ot PolyPI concentrations. In brain the extent of disappearance of PolyPI during the 10 min post-mortem period paralleled the content of gray matter: cerebral cortex greater than cerebellum greater than brain stem in all groups regardless of diet. Levels of PtdIns4P and PtdIns4,5P2 were decreased by 40% and 70% respectively in cerebral cortex of L- "0 min" samples. Deficits of both lipids in brain stem and cerebellum were 40-50%. In the L- 10 min samples, deficits were 20-30% in all three regions as compared with L+ 10 min levels, indicating the presence of a portion of both lipids affected only moderately by nutritional insufficiency. The effects on this relatively inert pool, much of it localized in myelin, were reversed on nutritional rehabilitation. The PolyPI pool lost post-mortem in L+ brain regions was practically absent in L- brain regions and was not restored in L-P+ animals. Thus, this study indicates that a metabolically labile pool, primarily located in gray matter structures, is more sensitive to nutritional deprivation during the pre-weaning period than the more stable pool. The precise role and function of these pools remain to be determined.

Animals↗

[Diagnostic value of sigmoidoscopic examination in diseases of the colon (author's transl)].

215 Cases out of 400 colosopic and 300 sigmoidoscopic examinations showed polypi and carcinomas. The polypi of 170 patients were located at a rate of 63,5% in the rectum and sigma area and of 36,5% in the proximal colon sections. Out of 45 carcinomas 80% could be localized in the rectum and sigma area and 20% in the further parts of the colon. Patients, if only sigmoidoscopically examined, showed polypi at a rate of 4,7% and carcinomas of 1,3%. For patients coloscopically examined polypi were found at a rate of 23,5% and carcinomas of 8% in the rectum and sigma area. 66% of all polypous changes and 82% of carcinomas were found with patients beyond 60 years of age. In 17 cases colitis ulcerosa, in 3 cases Morbus Crohn and in 3 cases of lipom could be established. The relatively high rate of pathological abnormities found in the upper colon section proves the diagnostic value of a total coloscopic examination. The recto-sigmoidoscopic examination therefore should be restricted to provisionary tests only.

Adult↗

Low affinity purinergic receptor modulates the response of rat submandibular glands to carbachol and substance P.

The effect of extracellular ATP on the intracellular calcium concentration ([Ca2+]i) in rat submandibular glands was tested. The dose-response curve for ATP was biphasic with a first increase in the 1-30 microM concentration range and a further increase at concentrations higher than 100 microM. Among ATP analogs, only benzoyl-ATP stimulated the low affinity component. ATP tau S blocked this response. All the other analogs tested reproduced the high-affinity low capacity response. Magnesium and Coomassie blue selectively blocked the low affinity component. High concentrations of ATP blocked the increase of the intracellular calcium concentration [Ca2+]i in response to 100 microM carbachol. By itself, substance P (100 pM-1 microM) increased the [Ca2+]i. One mM ATP potentiated the response to concentrations of substance P higher than 10 nM. This potentiation was reversed by extracellular magnesium. Carbachol 100 microM and substance P (100 pM-1 microM) increased the release of inositol trisphosphate (IP3) from polyphosphoinositides (polyPI). Activation of the low affinity ATP receptors did not activate the polyPI-specific phospholipase C but inhibited its activation by 100 microM carbachol (-50%) and by 100 nM substance P (-60% at 1 nM substance P and -40% at 100 nM substance P). Substance P induced a strong homologous desensitization: a preincubation with 1 nM substance P nearly completely abolished the response to 1 microM substance P. When the cells were exposed to ATP before the second addition of substance P, the purinergic agonist partially restored the response to the tachykinin without totally reversing the desensitization. It is concluded that two types of purinergic receptors coexist in rat submandibular glands; a high-affinity, low capacity receptor which remains pharmacologically and functionally undefined and a low affinity site, high capacity receptor of the P2z type coupled to a non-selective cation channel. The occupancy of these low affinity sites blocks the increase of the [Ca2+]i in response to a muscarinic agonist and the activation of polyPI-specific phospholipase C by carbachol and substance P. It potentiates the effect of high concentrations of substance P on the [Ca2+]i.

Adenosine Triphosphate↗

[Endoscopic diagnosis and therapy of colorectal tumours (author's transl)].

1. If endoscopy leads to the suspicion of an exulcerated and/or polypous carcinoma of the colon, surgical intervention is the primary therapy. Histological classification of the tumour should be effected by means of endoscopic biopsy. 2. (Familial) adenomatosis of the colon requires colectomy. 3. Broad-based polypi resembling a lawn where a large wound area must be expected by electrocoagulation (risk of perforation), and pediculate polypi of the (rare) size of 3 cm and more (risk of haemorrhage) should not be resected via endoscopy but by surgery. 4. Solitary or multiple polypi of the colon not covered by points 1 to 3 above, are primarily for reasons of diagnosis an indication for endoscopic polypectomy. Biospy in the case of adenomas to clarify the histological structure and to obtain qualitative and quantitative information regarding malignant degeration, must be discouraged (""partial diagnosis''.) 5. Basing on the current state of knowledge it is assumed that effective prohylaxis of cancer is achieved by the endoscopic removal of benign adenomas of the colon. 6. It is also assumed that effective cancer therapy can be realised by the endoscopic removal of adenomas which have already undergone malignant degeration (adenoma with severe cellular atypia, invasive differntiated adenocarcinoma in the head of the adenoma.)

Adenocarcinoma↗

[Patient with stomach polyps--a risk group for colorectal tumors? Haemoccult studies on 106 patients].

106 patients in whom from 1 to 4 years ago a gastric polyp had been removed were examined for occult blood in the feces (haemoccult test). It should be tested whether in carries of gastric polypi increasingly appear colorectal tumors. Altogether 15 patients with colorectal tumours were found among the 106 carriers of gastric polypi. In 11 patients a removal of an adenoma from the colon was performed already before the haemoccult-examination. With the help of the haemoccult-examination 2 carcinomas of the colon and 2 carriers of adenomas were newly recognized as well as 2 recidivations of adenomas. Carriers of gastric polypi should be regarded as risk group for colorectal tumours. The dispensary care must be extended not only to the stomach but also include a careful anamnesis with regard to colorectal tumours and the search for occult blood in the feces.

Colonic Neoplasms↗

Laparoscopic total colectomy for asymptomatic familial adenomatous polyposis.

A 20-year-old female patient with familial adenomatous polyposis diagnosed on the occasion of the screening of her family, which had a history of three deaths due malignant colic polyposis, was submitted to total colectomy by laparoscopic technique. Though the histopathological examination performed on two polypi excised by endoscopic technique did not evidence signs of malignant shift, total colectomy was performed, observing the oncological principles. The intervention was uneventful and postoperative course uncomplicated, the patient being socially reintegrated after three weeks. Follow-up examinations performed up to 18 months after the operation showed a favourable evolution and no development in the size and number of polypi.

Adenomatous Polyposis Coli↗

[Comparative clinical, histomorphological and immunological investigations into etiological aspects of polyposis nasi et sinuum (author's transl)].

43 patients with polyps affecting the nose and the sinuses were examined for immunological deficiencies on the basis of clinical, histomorphological and immunological findings. Constant histological findings were a chronic non-specific inflammation of varying intensity; immune-histologically a varyingly dense collection of Ig-producing cells with intracellular and extracellular immunoglobulins was observed. A determination of the immunoglobulins in the serum allowed no conclusion to be drawn as to the local condition of the mucosa. Hypertensitivity reactions played no role as a causal pathogenetic factor in the development of polyposis. In a third of the cases, however, polypi led to a secondary bronchial asthma. After the surgical removal of the polypi from the nose and paranasal sinuses, not only an improvement in nasal breathing and in the aeration of the sinuses was regularly achieved, but obstructive disorders of ventilation also disappeared.

Adult↗

Some remarks on nasal polyposis.

After a short historical and literature review the authors present their definition of nasal polyposis. The importance of CT scanning is stressed and the results of a CT-scan study of 350 patients with nasal complaints is presented. The authors discuss the incidence of sinusitis, presence of polypi and nasal anomalies in this population. Furthermore 111 biopsies of nasal polypi were studied and the cellular content, the ducts, glands, veins, aspect of the basal membrane and epithelial layer were described. As an oral ASA provocation test can be hazardous, the authors tested a nasal provocation test with acetylsalicylic acid. Although the test showed some interesting results, the reproducibility was poor. Finally the authors conclude that endoscopy and CT-scanning enable the diagnosis of nasal polyposis in an early stage of the disease.

Aspirin↗

[Single adenomatous polyp or adenocarcinoma of the rectum and sigmoid].

The problem of single adenomatous polypus and adenocarcinoma of rectosigmoid is debatable. Forty eight polypi with adenomatous structure were diagnosed and total polypectomy performed with 925 rectoromanoscopic examinations. In 6 of them, zones of malignization various in dissemination, were histologically confirmed. In two of the patients intestinal resection was performed, due to invasion of the malignization within the base of the polypus. The rest, four patients, with focal superficial malignization and the other 42 patients with "pure" adenomatous polypi are subjected to periodical rectoromanoscopic observations.

Adenocarcinoma↗

Gastric carcinoids. The Yale Experience.

OBJECTIVES: To document our experience with gastric carcinoids over the past decade and to identify lesion frequency and the existence of a relationship to low acid states. DESIGN: Retrospective case series. SETTING: Tertiary care referral center. PATIENTS: A consecutive sample of 16 patients with gastric carcinoids was evaluated over the last decade. Only two cases were recorded in the prior decade. Ages ranged from 30 to 93 years (mean, 65.9 years). There were eight men and eight women. Three patients were unavailable for follow-up. INTERVENTIONS: Therapy included total gastrectomy (n = 4), subtotal gastrectomy (n = 3), endoscopic polypectomy (n = 3), and endoscopic surveillance (n = 6). MAIN OUTCOME MEASURES: Pathobiological tumor characteristics and survival. RESULTS: All carcinoids were of gastric fundic origin. None of the patients exhibited the carcinoid syndrome. Chronic atrophic gastritis was the most frequently observed comorbid pathologic condition (63%). Half of the patients had multiple polypi. Mean follow-up was 4.7 years (n = 13). There were 10 survivors. The only related death occurred in a patient with a solitary tumor. CONCLUSIONS: Diagnosis of the complex and ill-defined entity of gastric carcinoid is increasing. This may be due to an increased awareness and increased upper gastrointestinal endoscopy rate rather than an increase in real incidence. Criteria for prediction of malignant progression are not available. Multiple gastric carcinoids associated with hypergastrinemia predominantly display nonaggressive behavior. Conservative gastric surgery may be appropriate therapy for such patients.

Adult↗

Adult intussusception in the tropics.

Thirty-two cases are reported of intussusception occurring in patients over the age of 12 years, diagnosed in Papua New Guinea in the 8 years from March 1973. Malignant disease was found in only 2 patients (6.3 per cent), and in 21 cases (65.5 per cent) no associated pathology was detectable. Benign inflammatory polypi were encountered in 7 patients (22 per cent). A high proportion of primary intussusceptions is characteristic of series reported from tropical countries. Many may be due to the abnormal motility associated with acute diarrhoeal illnesses. Due to the rarity of associated malignancy a policy of conservative operative management is justifiable in a tropical environment.

Adolescent↗

Incidence of synchronous and metachronous colorectal carcinoma.

Two hundred and twenty-three patients with colorectal carcinoma were treated consecutively at the University Hospital of South Manchester from May 1976 to January 1981. Twenty-four patients (10.7 per cent) were found to have more than one colorectal carcinoma. In 18 patients this was recognized either immediately or within 6 months of the initial diagnosis--synchronous carcinoma. In the other six cases a second carcinoma was found at a later time--metachronous carcinoma. The incidence of synchronous, and consequently the combined incidence of synchronous and metachronous carcinoma, was higher than previously documented. The anatomical distribution of the multiple carcinomas and the sex incidence in these patients was similar to that seen in patients with a single carcinoma of the large bowel. A high association of adenomatous polypi with multiple large bowel carcinomas was observed. The possibility of more extensive colonic resection in the younger patient with a favourable carcinoma is discussed.

Adult↗

[Histoautoradiographic studies of Billroth I-operated rat stomachs in relation to the postoperative interval. II. Histologic changes in the area of the anastomosis and its proliferation-kinetic behavior].

In a postoperative interval of 104 weeks' experience with 75 Wistar rats resected according to Billroth's 1st principle, the fourfold of standard of proliferative activity in addition to extended displacements and decompositions could be demonstrated. During 104 weeks of experience 8 animals developed in the anastomosed mucosa section adenomatous cystic glandular proliferations, 5 animals anastomotic polypi, 16 animals dysplastic gland areas and 10 animals showed anastomotic carcinomas. For these pathologic-anatomically outlined changes cellular proliferation was analysed by histoautoradiographic methods in parts of highest mitotic activity. The results were interpreted in dependence on their postoperative interval. In all pathologic-anatomical changes sources of strongest labelling could be found in the periphery. As most serious complication rats in experiment developed carcinoma in the anastomosed parts of mucosa. The peripheral sections of the carcinoma, so-called "front of invasion", showed regions of highest mitotic activity. Analysis of histoautoradiographic investigation in pathologic-anatomical change revealed modified proliferation kinetics in the sense of highly increased cell proliferation rates, which refer to the important role of the anastomotic region in the resected stomach.

Adenoma↗

Modulation of brain polyphosphoinositide metabolism by ACTH and beta-endorphin: structure-activity studies.

This study describes effects of ACTH1-24 and beta-endorphin on brain polyphosphoinositide metabolism in vitro. The interconversion of these polyanionic phospholipids was studied by incubation of a lysed synaptosomal fraction with [gamma-32P]ATP. Of the membrane phospholipids only PA, DPI and TPI became labeled. The reference peptide ACTH1-24 stimulated the formation of TPI and inhibited the production of PA. For effects on TPI formation both the sequences ACTH5-7 and ACTH10-16 were needed. Effects on PA formation required the sequences ACTH7-10 and ACTH10-16. The basic amino acids in ACTH10-16 seemed to be of crucial importance for the peptide effects. A stimulatory effect on DPI was visible when ACTH was shortened from the N-terminus, and the essential information was in ACTH7-10. beta-endorphin inhibited PA formation and this effect was abolished by C-terminal shortening to gamma-endorphin. Other fragments of the C-terminus of beta-LPH, including the enkephalins, were ineffective. It is concluded that the structure-activity relationship on TPI/PA formation correlates with a similar relationship obtained on excessive grooming behavior in vivo. A possible correlation between the effects on polyPI metabolism and opiate-like effects, and effects on extinction of active avoidance behavior in vivo is discussed.

Adrenocorticotropic Hormone↗

Fecal lipid chromatography--identification of an unusual fraction in relation to colon cancer.

The thin-layer chromatography of fecal lipids with revelation by phosphomolybdic reagent indicates the presence of an unusual fraction only in colon cancer patients. After isolation and identification, this fraction appears to be composed of coprostanol and its derivatives. The quantitative analysis of fecal neutral steroids in colon cancer patients compared to controls, patients with other digestive diseases and polypi shows a positive relationship between this fraction and colon cancer.

Adult↗

Chemotherapy of schistosomal colonic polyposis with oxamniquine.

Schistosomal polyposis of the colon is a common complication of schistosomiasis. In severe infections it may be associated with considerable morbidity. Surgery is associated with high morbidity and mortality. Niridazole therapy is of limited therapeutic value because of its hepatotoxicity but oxaminiquine has been found to be effective and safe. Several dosage regimens have been tried but a total dose of 40 mg/kg over two days in two equally divided doses has been found to have an effective therapeutic action on the polypi, with correction of the anaemia, hypoalbuminaemia and serum iron.

Adult↗

Introduction of polyphosphate as a novel phosphate pool in the chloroplast of transgenic potato plants modifies carbohydrate partitioning.

Potato plants (Solanum tuberosum L., cv. Désirée) were transformed with the polyphosphate kinase gene from Escherichia coli fused to the leader sequence of the ferredoxin oxidoreductase gene (FNR) from Spinacea oleracea under the control of the leaf specific St-LS1 promoter to introduce a novel phosphate pool in the chloroplasts of green tissues. Transgenic plants (cpPPK) in tissue culture developed necrotic lesions in older leaves and showed earlier leaf senescence while greenhouse plants showed no noticeable phenotype. Leaves of cpPPK plants contained less starch but higher concentrations of soluble sugars. The presence of polyphosphate in cpPPK leaves was demonstrated by toluidine blue staining and unambiguously verified and quantified by in vitro 31P-NMR of extracts. Polyphosphate accumulated during leaf development from 0.06 in juvenile leaves to 0.83 mg P g-1 DW in old leaves and had an average chain length of 18 residues in mature leaves. In situ 31P-NMR on small leaf pieces perfused with well-oxygenated medium showed only 0.036 mg P g-1 DW polyphosphate that was, however, greatly increased upon treatment with 50 mM ammonium sulfate at pH 7.3. This phenomenon along with a yield of 0.47 mg P g-1 DW polyphosphate from an extract of the same leaf material suggests that 93% of the polyphosphate pool is immobile. This conclusion is substantiated by the observation that no differences in polyphosphate pool sizes could be discerned between darkened and illuminated leaves, leaves treated with methylviologen or anaerobis and control leaves, treatments causing a change in the pool of ATP available for polyPi synthesis. Results are discussed in the context of the chelating properties of polyphosphates for cations and its consequences for the partitioning of photoassimilate between starch and soluble sugars.

Animals↗

Epidemiological study of p53 tumor suppressor gene mutations in patients from Luxembourg and the German Saar region with an advanced colorectal cancer using PCR-SSCP analysis.

Mutations in the p53 tumor suppressor gene are usually associated with an advanced development of colorectal cancer characterized by the transition from the adenoma to the carcinoma stage. We used the polymerase chain reaction (PCR) followed by single-strand conformation polymorphism (SSCP) analysis to screen for the presence of mutations in the p53 gene of patients from Luxembourg and the German Saar region with colorectal cancers at various developmental stages. While we detected no mutations in 16 colic polypi at an early to intermediate stage (adenoma), we revealed seven (13.7%) non-silent point mutations (transitions) in exons 5 to 9 of the p53 gene in 51 colorectal tumors at a late stage (carcinoma). In addition to confirming previous observations, these results show that PCR-SSCP analysis can provide both a sensitive and rapid method for the genetic determination of the histopathological stage of colorectal samples.

Adult↗