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Biomedical subjects

H Weiler

Publications and source records attributed to H Weiler.

At least 37 records · Page 2Linked to original sources

The basic helix-loop-helix transcription factor capsulin controls spleen organogenesis.

Formation of numerous internal organs involves reciprocal epithelial-mesenchymal signaling and subsequent patterning and growth of the organ primordium. Capsulin is a basic helix-loop-helix transcription factor expressed in mesenchymal cells that encapsulate the epithelial primordia of internal organs, including the kidney and lung, as well as the epicardium, which gives rise to the coronary arteries. Capsulin is also expressed in the mesothelium that gives rise to the spleen. We demonstrate that mice homozygous for a capsulin null mutation fail to form a spleen. The homeobox genes Hox11 and Bapx1, shown previously to be essential regulators of spleen organogenesis, and a lacZ reporter introduced into the capsulin locus, were expressed in the early splenic primordium, derived from the splanchnic mesoderm, of homozygous mutant embryos. However, this primordium failed to develop beyond an initial group of precursor cells and underwent rapid apoptosis. The phenotype of capsulin mutant mice demonstrates that capsulin acts within a subpopulation of splanchnic mesodermal cells to control an essential early step in spleen organogenesis that is likely to represent a point of regulatory convergence of the capsulin, Hox11, and Bapx1 genes.

Animals↗

Flaxseed ameliorates interstitial nephritis in rat polycystic kidney disease.

BACKGROUND: Flaxseed has demonstrated useful antiinflammatory properties in a number of animal models and human diseases. We undertook a study to determine if flaxseed would also modify clinical course and renal pathology in the Han:SPRD-cy rat. METHODS: Male Han:SPRD-cy rats were pair fed a 10% flaxseed of control rat chow diet for eight weeks from weaning. Tissue was harvested for analysis of cystic change, apoptosis, cell proliferation, and fibrosis. Tissue was also harvested for lipid analysis using gas chromatography. RESULTS: Animals thrived on both diets. Flaxseed-fed animals had lower serum creatinine (69 vs. 81 mumol/liter, P = 0.02), less cystic change (1.78 vs. 2.03 ml/kg, P = 0.02), less renal fibrosis (0.60 vs. 0.93 ml/kg, P = 0.0009), and less macrophage infiltration (13.8 vs. 16.7 cells/high-power video field) of the renal interstitium than controls. The groups did not differ in renal tubular epithelial cell apoptosis and proliferation. Lipid analysis revealed significant renal enrichment of 18 and 20 carbon omega 3 polyunsaturated fatty acids (total omega 6:omega 3 ratio 3.6 vs. 9.1, P < 0.0001). CONCLUSIONS: Flaxseed ameliorates Han:SPRD-cy rat polycystic kidney disease through moderation of the associated chronic interstitial nephritis. The diet alters renal content of polyunsaturated fatty acids in a manner that may promote the formation of less inflammatory classes of renal prostanoids.

Animals↗

[Elephant herpes virus--a problem for breeding and housing of elephants].

Herpesvirus infections which take a fatal turn on African elephants as well as on Asian elephants seem to occur increasingly not only in the USA but also in European stocks. The endotheliotropic herpesvirus causes a rapidly progressing and severe disease which makes any therapeutical effort unsuccessful and finally results in death of the animal, especially in young Asian elephants. As all attempts to culture the virus failed up to now, molecular biological procedures have to be used more often for diagnostical purpose together with the common methods of pathology, virology, and electronmicroscopical evaluation. This is a report on the case of 'KIBA', an eleven year old male elephant at the Zoological Garden Berlin, infected with the endotheliotropic elephants herpesvirus. 'KIBA' was born at the Zoo in Houston, Texas, and raised within his herd. Upon arriving in Berlin in November 1997 he adapted to the new premises and climate and new social circumstances without any problems. In June 1998 he already serviced three females of his new herd several times. In August 1998 he died after passing a peracute progression of the disease after residenting in Berlin for only 9 months. The dissection of the animal revealed some evidence on an agent damaging the endothelium. Major signs indicating this agent were bleedings in several serous membranes, mucosa and on the the right atrium, as well as other parts of the myocardium. Furthermore there have been ulcerations at various localisations of the whole digestive tract. Slightly basophilic intranuclear inclusion bodies have been found histologically in endothelial cells of different organ samples. An examination of altered organ-material by electronmicroscopy made some herpesvirus-like particles visible. A virological investigation first revealed evidence of giant cell formations with solitary basophilic intranuclear inclusion bodies in different cell cultures, however, without any distinct cytopathogenic effect. Supported by molecular biological procedures the infection of 'KIBA' could be verified as the elephants herpesvirus. By means of PCR and subsequent sequence analysis a DNA-sequence typical for the elephants herpesvirus could be obtained which showed an identity of 97% with the terminase sequence of the elephant herpesvirus described by American authors. The deduced amino acid-sequences were 100% identical. To the terminase of the human cytomegalovirus, the elephant sequence had an identity of 53% (similarity: 74%). Based on the cooperation of ILAT, Institute of Veterinary-Pathology/Free University Berlin, Robert-Koch-Institut Berlin, and Zoological Garden Berlin, the cause of 'KIBA's' death could be discovered immediately. Possible implications of this case especially on breeding and keeping elephants are discussed briefly.

Amino Acid Sequence↗

Effects of selenium deficiency on testicular morphology and function in rats.

For four generations rats were fed a low selenium diet (2-7 micrograms Se kg-1) or the same diet with 250 or 300 micrograms Se kg-1 added as selenite. In male rats of the first generation that had been fed the diets from the age of 20 days onwards, selenium depletion led to slightly delayed testis growth during pubertal development that was compensated for in the later stages of maturation. In adult rats fed the low selenium diet for nearly a year no changes in testicular mass and morphology were observed. The serum concentration of testosterone of 6-month-old, selenium-depleted animals was, however, slightly lower than that of adequately supplied controls, and the stimulation of testosterone secretion by administration of GnRH or LH resulted in a significantly less marked rise in the serum concentration of testosterone. From the second generation onwards the testis mass, expressed as a percentage of the body mass, decreased and in the fourth generation was less than 50% of that of the controls. The male gonads of fourth generation animals showed a severe bilateral atrophy, in which the seminiferous tubules were considerably reduced in diameter and almost entirely lined by Sertoli cells and a few stem cells. Differentiated spermatozoa could not be detected. The alterations were reversible and spermatogenesis was restored by feeding the selenium-adequate diet. The findings indicate that testicular morphology and functions are affected by severe selenium deficiency and that the element is necessary for testosterone biosynthesis and the formation and normal development of spermatozoa.

Animals↗

Absence of the blood-clotting regulator thrombomodulin causes embryonic lethality in mice before development of a functional cardiovascular system.

We have targeted the murine thrombomodulin (TM) gene in embryonic stem cells and generated embryos as well as mice with TM deficiency. The heterozygous TM-deficient (TM+/-) mice as compared to wild-type (TM+/+) littermates exhibit 50% reductions in the levels of TM mRNA and TM protein. However, TM+/- mice appear normal and are free of thrombotic complications. The homozygous TM-deficient (TM-/-) embryos die before embryonic day 9.5. An overall retardation in growth and development of TM-/- embryos is first evident on embryonic day 8.5 (8-12 somite pairs). However, no specific pathologic abnormalities are observed. These initial changes take place at a time when TM is normally expressed in the parietal yolk sac. The removal of embryonic day 7.5 TM-/- embryos from maternal decidua and their subsequent culture in vitro allow development to proceed to stages not observed in vivo (13-20 somite pairs) with the appearance of normal blood vessels in the visceral yolk sac and embryo. The results of our studies suggest that the failure of TM-/- embryos to survive at mid-gestation is a consequence of dysfunctional maternal-embryonic interactions caused by the absence of TM in the parietal yolk sac and demonstrate that the receptor is necessary for normal embryonic development in utero.

Animals↗

Endoscopic polypectomy and management of colorectal adenomas with invasive carcinoma.

BACKGROUND AND STUDY AIMS: Invasive carcinoma is found at histology in 2-5% of colorectal polyps removed under flexible endoscopy. The aim of this study was to confirm that histologically complete endoscopic polypectomy under favorable low-risk conditions is sufficient therapy for pT1 carcinoma, while tumors at or close to the margin of the polypectomy, and histological high-risk criteria, require surgical resection with lymphadenectomy. PATIENTS AND METHODS: Eighty-six patients with 87 pT1 carcinomas underwent polypectomy within a twelve-and-a-half-year period. Further treatment prospectively followed the above guidelines. The follow-up was documented. RESULTS: A local tumor residue was found in 5 of 34 patients who had undergone surgical resection for doubtful or incomplete polypectomy. Two patients were found to have nodal disease in the surgical specimen, only one of them harboring a high-risk carcinoma. Two further patients with high-risk carcinomas had tumor progression, despite postpolypectomy resections without local tumor residue or lymph-node infiltration, and died. One patient had a local tumor recurrence on follow-up endoscopy eight weeks after doubtfully complete polypectomy. He underwent resection, and had no further recurrence. No further manifestations of invasive carcinoma occurred after complete polypectomy of 42 patients with low-risk carcinomas. CONCLUSIONS: This study supports the view that complete endoscopic polypectomy is an adequate therapy for low-risk carcinoma: A modification of the follow-up regimen, with less frequent endoscopic controls, is justified.

Adenoma↗

[Skeletal findings in an adult dog recovering from osteodystrophia fibrosa].

In a 9-year-old male German Shepherd dog with a body weight of 37 kg which was euthanised because of a spinal meningioma, examination of the carcass revealed severe signs of degradation concerning the whole skeleton which were investigated by radiological, microradiological and pathologic-histological means. The skeletal alterations in form of systemic defects in corticalis and spongiosa in fact correspond to appearance and localisation of bone defects typical of fibrous osteodystrophia, but now are filled by conspicuous cell-poor matured collagenous connective tissue. In this connection it must be emphasised, that there are no osteoclasts detectable in the lacunae of degradation so that the disease process apparently has stopped.

Animals↗

[Paranasal sinus mycetoma with orbital involvement in a patient with AIDS].

A patient with AIDS was hospitalized with a left-sided face swelling and protrusion of the bulbus. After cranial computed tomography and fine-needle aspiration biopsy of the fossa temporalis we diagnosed a mycetoma; localisation and histology made an aspergilloma most probable. Antimycotic therapy led to complete remission of the symptoms. Post mortem we only could culture Candida albicans out of the abscess cavity.

AIDS-Related Opportunistic Infections↗

[Benign chondroma of the pancreas].

Fragments of a puncture cylinder were obtained from a pancreas tumour, using the ultrasound-guided fine-needle puncture. The tumour appears as an echo-poor, homogeneous structure suggesting good delineation against the adjoining tissue. Histological examination of the punch cylinder revealed a chondroma of the pancreas. Clinical and clinical pathology examinations (lipase, alpha-amylase, glucose, CEA, CA 19-9 in serum) were inconspicuous. Chondroma of the pancreas does not require specific treatment.

Aged↗

[Ultrasound-controlled percutaneous drainage of subhepatic liver abscess after conventional cholecystectomy].

From February 1984 to August 1991 subhepatic abscesses were detected by ultrasound in 7 patients with fever following conventional cholecystectomy. Cholecystectomy had been performed in all these patients 6 to 27 days previously. All patients had received antibiotic prophylaxis at the time of cholecystectomy. Three of the 7 patients were at first afebrile, later on again febrile. In the remaining 4 of the 7 patients antibiotic treatment was continued in the face of persistent fever. Percutaneous catheter drainage was performed in all patients. In all of the 7 cases the subhepatic abscesses resolved completely within 10 days to 7 weeks.

Aged↗

Increased prostaglandin PGE2 and 6-keto-PGF1 alpha immunoactivity in incubates of gastric mucosa and forestomach of nephrectomized rats.

Prostaglandin E2 (PGE2)- and 6-keto-PGF1 alpha-like immunoactivity was measured in incubates of forestomach and gastric corpus mucosa in (a) unoperated rats, (b) rats with sham-operation of the kidneys and (c) rats with bilateral nephrectomy. In addition the mean ulcer area in the forestomach and gastric mucosa was assayed in all three groups of rats. The PGE2- and 6-keto-PGF1 alpha-like immunoactivity in gastric mucosa incubates and 6-keto-PGF1 alpha in the forestomach incubates was almost the same in unoperated and sham-operated rats. Increased 6-keto-PGF1 alpha in the forestomach and of PGE2 and 6-keto-PGF1 alpha in the gastric mucosa was found in rats with bilateral nephrectomy before gastric lesions were seen. A higher mean ulcer area occurred in the forestomach and gastric mucosa 24-48 h after bilateral nephrectomy. We conclude, that the increased PGE2- and 6-keto-PGF1 alpha production by the gastric mucosa and forestomach was associated with the loss of normal renal tissue function. Despite the protection of PGE2 and PGI2 by gastric tissue, gastric lesions nevertheless occur in acute uraemic rats.

6-Ketoprostaglandin F1 alpha↗

[Cavernous liver hemangioma with arterio-portal fistula].

Evidence of a cavernous hemangioma of the liver with fistula between hepatic artery and the portal vein of a 52 year-old woman with colickly upper abdominal pain and ascites was obtained using Duplex-Doppler-ultrasound. The diagnosis was confirmed by selective arteriography. After ligation of the left hepatic artery clinical symptoms abated. The cavernous hemangioma was followed up over 7 1/2 years with ultrasound. Ultrasound has been shown to be a valuable test for diagnosis and follow up of cavernous hemangioma.

Angiography↗

[Double vertebral injury in a calf (case report)].

A double spinal cord trauma of an eight weeks old calf is reported, born on pasture from a heifer as a premature birth at the beginning of month 9. Observations made were rupture of intervertebral disk at the crossing of cervical to thoracic vertebrae followed by syndesmosis or synchondrosis resp., as well as a comminuted fracture of the 1st lumbar vertebra including both the adjoining vertebrae, with succeeding reactive callus formation. It is concluded that this traumatization has occurred during parturition. Motoric or sensory disturbances were observed neither.

Animals↗

Decreased prostaglandin E2 immunoactivity of gastric mucosa in portal hypertension.

PGE2-like immunoactivity was measured radioimmunologically in specimens from gastric corpus mucosa in (a) healthy subjects, (b) patients without liver disease in the absence or presence of gastric ulcer, and (c) patients with alcoholic cirrhosis in the absence or presence of gastric ulcer, further divided into subgroups without or with portal hypertension. The PGE2-like immunoactivity was almost the same in subjects without liver disease and in cirrhotic patients without portal hypertension. A significantly decreased PGE2-like immunoactivity was found in patients with portal hypertension, especially in cases of congestion in the mucosa. A further decrease of the PGE2-like immunoactivity could be found whenever gastric corpus ulcer was present. This decrease is statistically significant. We therefore concluded that a decrease in the PGE2-like immunoactivity in the gastric mucosa of cirrhotic patients is closely related to portal hypertension. Congestion in the mucosa, thought to be a relevant factor in the pathogenesis of the mucosal PGE2 deficiency, might also play a role.

Adolescent↗

Gastric mucosal PGE2 levels in gastric non-ulcer and ulcer patients with chronic renal failure or without renal diseases and in healthy subjects.

PGE2-like immunoactivity in mucosal specimens from gastric corpus and antrum was measured in individuals with chronic uremia or without renal diseases in absence or presence of gastric ulcerations and in healthy subjects. Regardless the group of patients, compared to normal mucosa, a significant decrease in PGE2-like immunoactivity (50-70%) was found in mucosa from atrophic, but not from superficial gastritis. Whenever patients of the control group or patients with renal diseases suffered from ulcers, PGE2-like immunoactivity, compared to nonulcer subjects, revealed a decrease of about 60-70% in the nonulcerated mucosa. Compared to nonulcerated mucosa, the tissue of the ulcer rim in all patients with gastric ulcer showed a relative increase in PGE2-like immunoactivity, eg, PGE2-like immunoactivity was twice as high in tissue from the ulcer rim. The output of PGE2-like immunoactivity into the gastric juice of subjects without renal diseases was comparable to that found in patients with chronic uremia in both basal and pentagastrin-stimulated conditions. We therefore conclude that gastric mucosal formation is probably not influenced by chronic uremia.

Adult↗

Effect of methotrexate on the release of prostaglandins E2, D2, and I2 from small intestine in the rat in vivo.

Intraperitoneal administration of methotrexate in a single dose of 40 mg/kg induces fluid accumulation in the small intestine of rats, significantly increasing jejunal PGE2 formation and simultaneously the amounts of PGE2 in the intestinal contents in vivo. Concomitantly, jejunal PGD2 and 6-keto-PGF1 alpha generation and the amounts of these prostaglandins in the intestinal contents were significantly lowered. However, PGD2 and 6-keto-PGF1 alpha jejunal release, and the amounts of these prostaglandins found in the intestinal contents, were already low after a sublethal dose (4 mg/kg) of methotrexate, whereas the jejunal release as well as the amounts in the intestinal contents of PGE2 were not altered. Fluid accumulation, the amounts of prostaglandins in the intestinal contents and jejunal release of prostaglandins are significantly inhibited by indomethacin. The increased jejunal synthesis of PGE2, with its enteropooling effect, may play a significant role in methotrexate-induced diarrhea in rats.

Animals↗

Gastric mucosal prostaglandin E2 levels in cirrhosis and portal hypertension.

Prostaglandin E2 (PGE2) tissue levels were measured, using radioimmunoassay, in specimens from the gastric antral mucosa in (a) healthy subjects, (b) patients without liver diseases in the absence or presence of gastric ulcers, and (c) patients with alcoholic cirrhosis in the absence or presence of gastric ulcers. These groups were divided further into subgroups with or without portal hypertension. PGE2 tissue levels in subjects without liver diseases were not significantly different from those of cirrhotic patients without portal hypertension. However, in cirrhotic patients with portal hypertension, the PGE2 content was significantly lower, especially in the presence of congestion in the mucosa (about 70-80%). When a gastric antral ulcer was present, a further statistically significant decrease of the PGE2 levels was observed. It was concluded that a decrease in the PGE2 tissue levels in the gastric mucosa of cirrhotic patients is related to the presence of portal hypertension. Congestion in the mucosa, as a pathogenetically relevant factor for mucosal PGE2 deficiency, may play a role.

Adult↗