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Biomedical subjects

R Waldherr

Publications and source records attributed to R Waldherr.

At least 217 records · Page 12Linked to original sources

Stimulation of chemically induced rectal carcinogenesis by chronic ethanol ingestion.

The effect of chronic ethanol administration on 1, 2-dimethylhydrazine-induced rectal carcinogenesis was investigated in 32 paired male Sprague-Dawley rats fed a nutritionally-adequate liquid diet containing 36% of the total calories as either ethanol or isocaloric carbohydrates. Chronic ethanol ingestion increased the total number of rectal tumors significantly (17 vs 6; P less than 0.02), whereas no cocarcinogenic effect of ethanol was observed in other parts of the intestine. Alcohol did not influence tumor size or histopathology. A 47% increase in the activity of mucosal alcohol dehydrogenase in the distal colorectal region was found between chronically-ethanol-fed rats and pair-fed controls (0.241 +/- 0.019 vs 0.164 +/- 0.020 mumol/mg of protein/hr; P less than 0.01). This could in part explain the cocarcinogenic effect of alcohol in this tissue. Faecal bile acids, however, do not play a role as promotors of rectal carcinogenesis under the present experimental conditions. The results give experimental support to the epidemiologic findings of an increased incidence of rectal cancer in the alcoholic.

Adenocarcinoma↗

The low density lipoprotein and low density lipoprotein receptors and their possible importance in the pathogenesis of atherosclerosis.

In man and in experimental animals, elevations in plasma cholesterol lead to premature atherosclerosis. It is likely that the cholesterol-rich low density lipoprotein (LDL) plays a keyrole in atherogenesis. LDL accumulates in patients with familial hypercholesterolemia (FH), a genetic syndrome associated with a defective LDL receptor in parenchymal cells and premature atherosclerosis. Monocytic/macrophage-like cells invading the vessel wall are becoming enriched with cholesteryl ester and concentrating in the early atherosclerotic lesion. Modification of LDL stimulates the uptake of cholesterol by macrophages in vitro leading to the conversion of the cells to lipid laden foam cells. Because of this phenomenon recent investigations were focussing on the lipid metabolism of macrophages. In vitro studies have demonstrated that macrophages have specific cell surface receptors for modified forms of LDL. It was suggested that these scavenger receptors could mediate foam cell formation in vivo, too. In vivo analysis by sequential scintiscans revealed that the liver is accumulating most actively modified LDL, possibly acting as a sieve for atherogenic lipoproteins. The putative liver receptor for modified (= atherogenic) LDL was characterized as a membrane protein of 220 000 to 250 000 D by ligand blotting.

Acetylation↗

Hypertension in mesangial IgA glomerulonephritis.

Blood pressure in 75 patients with IgA nephropathy (IgA-GN), confirmed by renal biopsy, was related to clinical, immunological and morphological findings. The findings were compared with an age-matched control group of patients with non-IgA-GN. Overall prevalence of hypertension (HT) was similar in IgA-GN and non-IgA-GN (38.7% vs 38.2%). The presence of HT in IgA-GN was related to age, renal function, immunohistological pattern and degree of glomerular sclerosis or vascular lesions respectively. No correlation was found between HT and elevated serum IgA, circulating IgA immune complexes and IgA skin deposits. The current observations underline the value of hypertension for predicting development of renal failure. Vascular lesions are not only strongly correlated with, but may even precede development of, hypertension as confirmed by longitudinal observations.

Adolescent↗

Acute renal failure in an infant with partial deficiency of hypoxanthine-guanine phosphoribosyltransferase.

A three week old boy presented with pneumonia, weight loss, metabolic acidosis and renal failure (serum creatinine 3.1 mg/100 ml, uric acid 11.5 mg/100 ml). Renal biopsy revealed severe crystal nephropathy. Low activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT) in erythrocytes and fibroblasts suggested a partial deficiency of the enzyme. A family study proved the mother to be heterozygous and the maternal grandfather to be hemizygous for HPRT deficiency. The grandfather developed gouty nephropathy and uraemia. The propositus was treated with allopurinol and kept on low purine diet and high fluid intake with sodium bicarbonate. Thereafter GFR gradually improved. At the age of two and a half years, growth and psychomotor development were normal, but ultrasound examination still revealed a dense renal parenchyma. Partial HPRT deficiency is a newly recognised treatable form of renal failure in the newborn.

Acute Kidney Injury↗

[Spontaneous parotid gland infarct].

Infarction of the parotid gland after surgery is caused by local ischaemia of the glandular tissue. The pathohistological changes are similar to those of necrotizing sialometaplasia of the minor salivary glands. A case of spontaneous infarction of the parotid gland in a 77 year old man is presented. The clinical appearance, sialometric, sialochemical, sialographic, cytological and microscopic features are described. The similarity of the morphological pictures of necrotizing sialometaplasia and squamous cell carcinoma and the resulting difficulties for differential diagnosis are discussed.

Aged↗

[Systemic light-chain disease as a complication of plasmacytoma].

An asymptomatic multiple myeloma of the kappa-light chain type was found in a patient with nephrotic syndrome and renal insufficiency. Light microscopy showed nodular glomerulosclerosis of the kidney similar to diabetic glomerulosclerosis. Diabetes mellitus could not be demonstrated. kappa-Light chain deposits could be shown by immunohistology in the mesangium and the glomerular and tubular basal membrane. In addition, massive kappa-light chain deposits in the sinusoidal walls of the liver and at the dermoepidermal junction of the skin and in the corium were found.

Antineoplastic Combined Chemotherapy Protocols↗

Virus-binding activity of fibronectin: masking of hepatitis A virus.

Human plasma fibronectin interacts with viruses. When fibronectin-containing human sera negative for antibodies to hepatitis A virus (HAV) were added to suspensions of HAV, radioimmunological detection of HAV was reduced. This masking effect seemed to depend on the fibronectin concentration of the sera: plasma fibronectin purified by cryoprecipitation and affinity chromatography showed a masking effect on purified HAV which was dependent on the concentrations of fibronectin and HAV. Fibronectin peptides were obtained by subtilisin digestion: the non-collagen-binding regions of the fibronectin molecule were involved in the binding of HAV. We conclude that fibronectin has a virus-binding activity which interferes with radioimmunological methods for virus detection, and may contribute to the frequent transmission of hepatitis viruses by blood products enriched in fibronectin.

Adult↗

Plastic filing from dialysis tubing induces prostanoid release from macrophages.

Multiorgan, abnormalities in dialysis patients (for example, hepatosplenomegaly, granulomatous hepatitis, cytopenia from hypersplenism) have recently been ascribed to the loading of macrophages (MO) with silicone particles released from the pump segment of dialysis tubing. In the present study, the effect of chronic intravenous or intraperitoneal loading of rats with silicone, polyvinylchloride (PVC) and polyurethane (PU) particles on arachidonic acid metabolism of peritoneal MO and splenic cells was examined in vitro. Intravenous injections of silicone, PVC, or PU particles caused accumulation of the material within the lysosomes of MO of spleen, liver, and lung. Spontaneous release of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) was significantly increased in peritoneal MO of rats injected with silicone, PVC, or PU (Control: 4.27 +/- 0.85 ng PGE2/ml/24 hr; silicone 51.9 +/- 13.2; PVC 57.5 +/- 10.6; PU 28.8 +/- 2.3). Zymosan or LPS stimulated PGE2 release from control MO, but caused no consistent further elevation of high basal PGE2 release from MO after particle loading. Furthermore, increased spontaneous and stimulated TXB2 release was also observed in spleen cells of rats given intravenous injection of silicone particles. It is concluded that storage of plastic particles (silicone, PVC, and PU) by macrophages stimulates arachidonic acid metabolism.

Animals↗

Multicystic transformation of kidneys in chronic renal failure.

With real-time sonography, 120 nondialyzed uremic patients prior to hemodialysis, 108 patients on maintenance hemodialysis and 9 patients postdialysis after successful homotransplantation were examined for the presence of renal cysts. Even in incipient renal failure, multiple cysts were demonstrable in some patients (at a serum creatinine of 3 mg/dl in 22% of patients), particularly in patients with analgesic nephropathy. When hemodialysis was started (serum creatinine approximately 10 mg/dl), 35% of the patients had multiple cysts. On hemodialysis, the prevalence, number and size of cysts rose progressively with time. After 8 years of hemodialysis, 92% of the patients had multiple cysts. However, enlargement of the kidneys was observed in only 2/108 patients. No major clinical complications were noted with the possible exception of 1 case of renal cell carcinoma. No correlation was noted between hematocrit and presence or extent of cystic transformation, but the 2 patients with cystic enlargement of the kidneys were polyglobulic. In 8/9 patients after transplantation, cysts were demonstrable in the patient's own kidneys after a median follow-up of 16 months. On light microscopy, cysts were lined by cuboidal or columnar epithelial cells with frequent papillary or adenomatous proliferations. The cyst lumen was filled with amorphous or lamellated organic material, which exhibited microfibrillar structure on electron microscopy. One kidney examined after ex vivo perfusion fixation showed multiple interconnected cavities on scanning electron microscopy. Ultrastructural studies showed epithelia with either the characteristics of proximal tubular cells (i.e. numerous microvilli, interdigitations and abundant lysosomes or mitochondria) or distal tubular cells (i.e. highly interdigitating processes) or finally collecting duct cells (i.e. no interdigitations and few microvilli).

Acute Kidney Injury↗

Enhancement of 1,2-dimethylhydrazine-induced rectal carcinogenesis following chronic ethanol consumption in the rat.

The incidence, distribution, size, and histopathology of grossly visible intestinal tumors induced by the parenteral administration of 1,2-dimethylhydrazine dihydrochloride were examined in 32 paired rats fed a nutritionally adequate liquid diet containing 36% of total calories either as ethanol or isocaloric carbohydrates. The liquid diets were begun 4 wk before the first of four weekly injections of 1,2-dimethylhydrazine dihydrochloride. At the time of the subcutaneous application of the procarcinogen, liquid diets were omitted for 3 wk, and were replaced by a standard laboratory diet. This feeding schedule was repeated four times, and after 32 wk the animals were killed. Chronic ethanol ingestion increased the total number of rectal tumors significantly (17 vs. 6, p less than 0.02). However, alcohol had no effect on tumor size or histopathology. Chronic ethanol ingestion did not exhibit any cocarcinogenic effect in tissues other than the rectum. A 47% increase in the activity of mucosal alcohol dehydrogenase in the distal colorectum was found between chronically ethanol-fed rats and pair-fed controls (0.241 +/- 0.019 vs. 0.164 +/- 0.020 mumol X mg protein-1 X h-1, p less than 0.01). This could in part explain the cocarcinogenic effect of alcohol in this tissue. Fecal bile acids, however, do not play a role as promoters of rectal cancer under the present experimental conditions. The data give experimental support to the epidemiologic findings of an increased incidence of rectal cancer in the alcoholic.

Adenocarcinoma↗

Idiopathic de Toni-Debré-Fanconi syndrome with absence of proximal tubular brush border.

In a girl with idiopathic de Toni-Debré-Fanconi syndrome associated with psychomotor retardation, severe renal tubular dysfunction was observed from the first day of life. At the age of 21/2 and 4 years the glomerular filtration rate (GFR) was only 60 ml/min/1.73 m2. No tubular transport of glucose, phosphate, paraaminohippurate and amino acids could be demonstrated. The tubular handling of uric acid, potassium and calcium, was also disturbed. Renal net acid excretion was zero at a plasma bicarbonate level of 14 mmol/l. Urinary osmolality ranged between 88 and 680 mosmol/kg. During hypotonic saline diuresis GFR decreased further; a GFR of 19 ml/min/1.73 m2 was accompanied by a fractional distal sodium delivery of 96.5% and a fractional free water clearance of 73%. In a renal biopsy specimen the proximal tubular cells showed variations in height with dedifferentiation and a widespread absence of brush border on electron microscopy. This formerly undescribed tubulopathy offers a unique chance to investigate glomerulo-tubular balance, adaptive mechanisms of distal tubular transport and renal metabolism under conditions where an apparently unchanged ultrafiltrate is offered by the proximal tubule to the loop of Henle and to a primarily intact distal tubule.

Amino Acids↗

Deposition of polymeric IgA1 in idiopathic mesangial IgA-glomerulonephritis.

IgA deposits in kidney and skin biopsies from patients with idiopathic mesangial IgA-glomerulonephritis were characterized with immunofluorescence microscopy using monoclonal antibodies against the IgA subclasses IgA1 and IgA2. IgA1 was the major constituent in all biopsy specimens. Double immunofluorescence microscopy showed that IgA deposits were constantly associated with J-chain. Secretory component was never found in the deposited material. In vitro fixation of free secretory component, however, was observed in some biopsies. These findings indicate that most if not all of the deposited IgA in patients with idiopathic IgA-glomerulonephritis is polymeric in nature.

Adolescent↗