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Biomedical subjects

S Shibolet

Publications and source records attributed to S Shibolet.

At least 19 recordsLinked to original sources

The multiplicity of atherosclerotic risk factors corresponds to the appearance of increased leukocyte count in the peripheral blood: relevance to the pathogenesis of the disease.

White blood cells may have a role in the aetiopathogenesis of atherosclerosis disease in patients with risk factors for this disease. We examined the white blood cell count in a group of 331 patients and controls of the same age group (139 women and 192 men), the numbers of individuals with no, one, two or more atherosclerotic risk factors being 29, 47, 35 and 28 for women and 50, 45, 68 and 29 for men, respectively. The risk factors included were hypertension, hyperlipidaemia, current smoking and diabetes mellitus. A stepwise increment in the white blood cell count was found in both women and men, the respective values for no, one, two or more risk factors being 6.3 +/- 1.5, 7.6 +/- 1.9, 7.5 +/- 1.8, 7.3 +/- 1.4 and 6.6 +/- 1.6, 6.9 +/- 1.9, 7.4 +/- 2.1, 8.1 +/- 2.6 (absolute number of cells per cm x 103). The one-way analysis variance was found to be significant for both women (P=0.01) and men (P=0.01), as well as the entire cohort (P=0.03). We conclude that the multiplicity of risk factors for atherosclerosis is associated with the appearance of an increased number of white blood cells in the peripheral blood. These findings might represent an enhanced inflammatory response in these individuals and at the same time reveal a potential harmful role of the cells in the aetiopathogenesis of the disease.

Analysis of Variance↗

Distribution of polysaccharide side chains of lipopolysaccharide determine resistance of Escherichia coli to the bactericidal activity of serum.

The lipopolysaccharide (LPS) of serum-sensitive strains of Escherichia coli was compared with LPS derived from serum-resistant clones. Polysaccharide O-antigen side chains (PSSC) of LPS from serum-resistant clones contained 12%-40% more of the longer carbohydrate molecules (L-PSSC) than did LPS from serum-sensitive parent strains; in contrast, 12%-27% more of the shorter PSSC (S-PSSC) were found in LPS from serum-sensitive strains. The sensitivity or resistance to the bactericidal activity of human serum correlated with the distribution and the length of PSSC fractions of LPS. This was demonstrated in a liposome model in which LPS was incorporated into simulated bacterial membranes. The incubation of serum with liposomes incorporated with various ratios of S-PSSC-to-L-PSSC concentrations resulted in liposomal lysis at S-PSSC-to-L-PSSC ratios greater than 2:1. These findings demonstrate the importance of the length of carbohydrate side chains of LPS in determining sensitivity or resistance to the bactericidal activity of human serum.

Blood Bactericidal Activity↗

Effects of endotoxin-associated protein on hematopoiesis.

Endotoxin-associated protein (EAP), a gram-negative bacterial cell wall component, was evaluated for its effects on hematopoietic colony formation in vitro. Colony-stimulating activity, induced by EAP on circulating and bone marrow progenitor cells, was found to be partially mediated by T cells and augmented by interleukin-3. The addition of anti-human interleukin-1 (IL-1) antibodies reduced EAP activity, suggesting that EAP may induce IL-1 production. However, EAP was shown to promote the growth of mature progenitor cells independently, unlike the effects of IL-1 on the hematopoietic system. These studies demonstrate that bacterial components other than lipopolysaccharide, such as EAP, may have hematopoietic activity.

Bacterial Proteins↗

Restoration of in vitro hematopoiesis in B-chronic lymphocytic leukemia by antibodies to tumor necrosis factor.

Hematopoiesis was evaluated in 15 B-CLL patients using the mixed colony formation assay. The mean growth of all types of colonies in B-CLL peripheral blood was significantly lower than that of 10 normal controls (p less than 0.05). To investigate whether TNF is the cytokine involved in the reduced growth of hematopoietic progenitors in B-CLL, neutralizing anti-TNF antibodies (anti-TNF Abs) were added to the cultures. Anti-TNF Abs optimized in vitro hematopoiesis in 11 out of 15 B-CLL patients and a significant growth increase in all types of colonies was noted as compared to baseline cultures (p less than 0.05). In patients with stage IV disease, the increase in both mixed and erythroid colonies was more prominent than in patients with earlier disease stages. This optimization of growth was also observed in normal control cultures containing accessory cells. However, high TNF levels were measured in conditioned media from CLL patients and suppressed normal bone marrow hematopoietic progenitors growth. In contrast no TNF was detected in normal conditioned media. It is concluded that TNF and other cytokines, among them IL-3, play a role in the regulation of hematopoietic function in some B-CLL cases. These findings may have clinical applicability.

Aged↗

Increased 25-hydroxyvitamin D levels in portal blood following cholecystokinin injection in the dog.

To establish whether an enterohepatic circulation of the metabolites of vitamin D exists, polyethylene catheters were cannulated into the portal vein of dogs. The dogs were then starved for 24 h and injected with cholecystokinin (CCK) to induce gall bladder contraction. At various time intervals thereafter blood samples were collected from the portal and the saphena veins, and sera prepared and analyzed for the metabolites of vitamin D. The serum levels of 25-hydroxyvitamin D [25(OH)D] were found to be significantly higher in the portal blood when compared with levels in peripheral blood following CCK injection. Since portal blood collects nutrients absorbed from the gut and as the dogs were starved for 24 h prior to blood collection, the only source of the increased concentrations of 25(OH)D in portal blood is likely to be bile. These findings support the notion that an enterohepatic circulation of 25(OH)D does exist under normal physiological conditions.

Animals↗

The importance of creatine kinase determination in identifying acute myocardial infarction among patients complaining of chest pain in an emergency room.

The contribution of serum creatine kinase (CK) levels to the diagnosis of acute myocardial infarction (AMI) in an emergency room was studied in 252 patients presenting with chest pain. Thirty percent were ultimately diagnosed as having AMI. The electrocardiogram (ECG) identified 66% of patients with AMI who were evaluated within 4 h of onset of symptoms; while CK serum levels were elevated in only 9%. Among patients evaluated more than 4 h after the onset of symptoms, the ECG was helpful in diagnosing AMI in only 36.6%, while serum CK levels were high in 63.4%. CK testing added significantly to the diagnosis of AMI in patients already studied by ECG. We suggest that determination of serum CK levels in the emergency room is of value in the evaluation of patients complaining of chest pain 4 or more hours after the onset of symptoms.

Adult↗

Multiple neuropathic arthropathy in a patient with syphilis.

An unusual case of neuropathic arthropathy in a patient with tabes dorsalis is presented. The special feature consisted of multiple joint involvement in the upper limbs and spine. This uncommon location of Charcot joints can probably be attributed to the patient's occupation which involved heavy strains on his upper limbs.

Arthropathy, Neurogenic↗

Allopurinol-induced toxic epidermal necrolysis.

An erythematous eruption with itching developed in an 84-year-old man 4 days after therapy with allopurinol was initiated. The diagnosis of toxic epidermal necrolysis, suspected when separation of the epidermis was noted, was confirmed by skin biopsy. This is the third reported case that can be attributed exclusively to allopurinol and the first patient who did not die.

Aged↗

Development of Hodgkin's disease in the course of liver cirrhosis and impaired monocyte function.

The monocyte function, as measured by phagocytosis and killing of Candida albicans and Candida pseudotropicalis by peripheral blood monocytes, was found impaired in a patient with cirrhosis of the liver on two separate determinations before the occurrence of bleeding from oesophageal varices. Unexpectedly, Hodgkin's disease was diagnosed in enlarged abdominal lymph nodes found on the occasion of an emergency portocaval shunt operation.

Candida↗

Fecal loss of cholecalciferol in gastrectomized rats.

Rats were gastrectomized, and the intestinal absorption and fecal excretion of cholecalciferol were studied following the administration of radioactive cholecalciferol, either by subcutaneous injection or with the aid of a gastric tube. From measurements of radioactivity in feces and sera it has been possible to establish that gastrectomy in rats results in impaired intestinal absorption and increased fecal excretion of cholecalciferol. These findings indicate that gastrectomy alters the nutritional status of vitamin D, and may explain the high incidence of osteomalacia as a complication of gastrectomy.

Animals↗

Amyloidosis associated with renal cell carcinoma of the AA type.

Amyloid fibrils were found at postmortem examination in a 70 year old woman with generalized amyloidosis associated with renal carcinoma (hypernephroma). Clinically, her amyloid disease presented as nephrotic syndrome. It was demonstrated by electrophoretic and amino acid sequence analysis studies that the amyloid fibrils contained AA protein identical to that found in amyloidosis associated with chronic inflammatory and infectious diseases as well as in the genetic form of familial Mediterranean fever.

Adenocarcinoma↗

Intestinal loss of vitamin D3 metabolites in rats with cirrhosis of the liver.

The metabolism of cholecalciferol (vitamin D3) was studied in cirrhotic and in control rats that were either depleted of or supplemented with vitamin D3. The vitamin was supplemented by s.c. injections of radiolabeled cholecalciferol at doses which meat the daily nutritional requirements of rats. Excretion of vitamin D3 metabolites in the feces of the cirrhotic rats was greater than that in the control rats. Fecal excretion consisted mainly of vitamin D3 ester the unchanged vitamin D3 and 25-hydroxyvitamin D3. It is suggested that one of the causes for vitamin D3 depletion in cirrhosis of the liver is fecal loss.

Animals↗

Typhoid hepatitis with immunoglobulins and complement deposits in bile canaliculi.

Documented typhoid fever in a 26-year-old patient was complicated by acute hepatitis with unusually profound jaundice. Liver biopsy revealed focal cell necrosis, mononuclear cell infiltration. Kupffer cell proliferation, and mild cholestasis. Immunofluorescent studies of the liver biopsy revealed deposits of IgG, IgA, IgM, and C3 in the bile canaliculi, suggesting a role for damage by immune complexes in typhoid hepatitis.

Adult↗

Impaired monocyte function in liver cirrhosis.

Monocyte function in patients with cirrhosis of the liver was measured by phagocytosis and killing of Candida pseudotropicalis and C albicans. Both variables were significantly decreased in the patients compared with controls. Control monocytes exposed for two hours to patients' serum showed a significant decrease in intracellular killing compared with control monocytes incubated in autologous serum. This suggests the presence of an inhibiting factor in the patients' serum. This inhibitory factor passed through a dialysis membrane that permitted the passage of molecules of less than 12 000 daltons. Treating monocytes from patients with trypsin significantly increased phagocytosis, indicating that the possible inhibitory factor was attached to the monocyte surface. Metabolism of monocytes during phagocytosis as determined by chemoluminescence was significantly lower in monocytes from patients compared with controls, indicating metabolic impairment. Monocytes are a component of the monocyte-macrophage system, which includes Kupffer's cells. Impairment of the function of these cells, which have a pivotal role in clearing portal blood, might well be extremely important in the development of chronic liver disease.

Adult↗