[153Sm-EDTMP in a patient suffering from colon cancer with bone metastasis].
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Adenocarcinoma↗
Biomedical subjects
C Nadal
Publications and source records attributed to C Nadal.
Nonregenerative stimulation of hepatocyte proliferation in the rat: variable effects in relation to spontaneous liver growth; a possible link with metabolic induction.
Three procedures were used to stimulate hepatocyte proliferation in the rat without reducing liver mass, resulting in a supplementary growth which differs from the regenerative growth observed after loss of liver mass by hepatectomy or toxic necrosis. They were: (a) the ingestion of cyproterone, a cytochrome P450 inducing drug (b) the injection of an irritant which provokes glycogenesis and synthesis of acute-phase proteins (c) the injection of albumin-bound bilirubin leading to elimination of glucuronated bilirubin in bile. This ensuing supplementary growth was studied in the rat under several conditions of hepatic proliferation: 1. In normal adult rats, in which hepatocyte proliferation is very low, the effect on proliferation was either weak or undetectable. 2. In suckling rats, with a rapid body and liver growth, all the stimulants provoked a synchronized wave of proliferation with a steep increase of the percentage of S-phase hepatocytes from 4.5% in controls to 15-30% in treated rats. This increase was followed by a compensatory period of low proliferation during which a treatment with a second stimulant was much less effective. 3. In 2/3 hepatectomized adult rats, the proliferation induced by cyproterone was higher than the spontaneous regenerative proliferation alone and additional to it during all of the regenerative process. The proliferation induced by acute inflammation was competitive with the synchronous spontaneous proliferation during the early period of synchronized proliferation following surgery, suggesting that both are similar acute responses. Differently, during the late period of lower and unsynchronized regenerative proliferation, the proliferation provoked by acute inflammation was additional to the spontaneous one. A stimulation of proliferation by injection of the albumin-bilirubin complex was observed during the late period after 2/3 hepatectomy. The highest level of stimulation occurred when the liver growth and the hepatocyte proliferation were already high. This suggests that these stimulants are not complete mitogenic stimuli and need cofactors which are present during the spontaneous growth or, alternatively, that the effect of stimulants is opposed by an inhibitory mechanism present in the adult rat.
Acute-Phase Reaction↗
Cutaneous granulomatous lesions in common variable immunodeficiency: complete resolution after intravenous immunoglobulins.
A 64-year-old man with common variable immunodeficiency developed a persistent papulonodular ulcerative eruption on the right leg. Histopathological examination disclosed a chronic inflammatory infiltrate with central necrosis and palisading granuloma. Repeated microbiological (bacteriological, mycological and mycobacteriological) studies failed to isolate any microorganism. After treatment with intravenous immunoglobulins, a progressive resolution of the skin lesions was observed with a complete clearing after 10 months. Clinicopathological features and therapeutic approaches of sterile granulomatous lesions associated with primary immunodeficiencies are reviewed.
Common Variable Immunodeficiency↗
Multiple follicular hamartomas with sweat gland and sebaceous differentiation, vermiculate atrophoderma, milia, hypotrichosis, and late development of multiple basal cell carcinomas.
We describe a 46-year-old woman with multiple symmetrical papulocystic lesions on the face, neck, chest, back, and upper arms since childhood. Vermiculate atrophoderma, entropion, and progressive loss of eyelashes was also noted. Since the age of 30, 12 basal cell carcinomas have developed on the face. Histopathologic examination revealed multiple anastomosing nests and strands that arose from the lower part of a hair follicle in early lesions. In more advanced lesions, multiple keratinizing microcysts within a moderately sclerotic stroma were noted in the upper and mid dermis. In some biopsy specimens, focal areas showing sweat gland (ductal) and sebaceous differentiation were also observed. Basal cell carcinomas developed from the basaloid component of the hamartomatous proliferation.
Atrophy↗
Bullous pemphigoid associated with acute glomerulonephritis.
We report an 82-year-old man who presented with bullous pemphigoid and who later developed an acute glomerulonephritis with the histopathological and immunofluorescence pattern of a postinfectious glomerulonephritis. Antibodies directed against 230 and 180 kDa bullous pemphigoid antigens were detected in the patient's serum by means of the immunoprecipitation technique. Staphylococcus aureus and methicillin-resistant S. aureus were isolated from the patient's skin. We consider that in this particular patient the cutaneous infection played a part in the development of the kidney complication.
Acute Disease↗
Brooke-Spiegler syndrome variant: segregation of tumor types with mixed differentiation in two generations.
Brooke-Spiegler syndrome (BSS) is an autosomal dominantly inherited disease characterized by the development of multiple trichoepitheliomas and cylindromas. Other lesions have been reported to occur in patients with BSS, including parotid basal cell adenomas, milia, organoid nevi, basal cell carcinomas, and spiradenomas. Spiradenomas and cylindromas have so many features in common that they have been regarded as polar extremes belonging to a spectrum of cutaneous adnexal neoplasms. We report on a 61-year-old woman with multiple spiradenomas on the scalp and periauricular areas and her 28-year-old daughter, with multiple facial trichoepitheliomas. Occasional features of pilar and ductal differentiation were found in tissue specimens of tumors from the mother and daughter, respectively. Co-existence of multiple spiradenomas and trichoepitheliomas and segregation of the predominant type of tumor in different members of a family with BSS have been reported occasionally, but never, to our knowledge, in combination. The presence of mixed differentiation in tumor specimens from both patients provides additional evidence in support of the folliculosebaceous apocrine unit (FSAU) hypothesis. Mutations in genes regulating proliferation and differentiation of putative stem cells of the FSAU would give rise to different combinations of adnexal skin tumors as well as to other neoplasms.
Adult↗
Intraepidermal IgA pustulosis associated with monoclonal IgA gammopathy in an HIV-infected patient.
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Adult↗
[Myositis caused by Pleistophora in a patient with AIDS].
The third case in the literature is reported of an infection produced by Pleistophora. The clinical detail of the three cases are discussed. Two of the patients-including the reported one-were infected by HIV. All patients suffered from myositis with fever, resting and at palpation myalgia, and progressive weakness. Blood tests showed anaemia and high levels of muscle enzymes. Necrotic muscle fibrosis induced disabling contractures. Diagnosis was obtained by detecting the protozoon in a muscle biopsy. The spores may be detectable by means of different staining methods at light microscopy although electron microscopy remains the most reliable technique. Since this is such a rare condition there is no known treatment. Whether the albendazole could be as useful as occurs in patients infected by other genera of microsporidia in still uncertain.
Acquired Immunodeficiency Syndrome↗
Carbamazepine-induced drug rashes: diagnostic value of patch tests depends on clinico-pathologic presentation.
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Adult↗
Systemic contact dermatitis from 5-fluorouracil.
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Antimetabolites, Antineoplastic↗
Imaging of pulmonary-cutaneous disorders: matching the radiologic and dermatologic findings.
Dermatologic lesions are often associated with pulmonary disorders and vice versa. Diseases with pulmonary and cutaneous manifestations can be divided into four major categories: (a) congenital and developmental disorders with cutaneous-pulmonary manifestations (Ehlers-Danlos syndrome, generalized elastolysis, yellow nail syndrome, neurofibromatosis, hereditary hemorrhagic telangiectasia); (b) primary dermal diseases with associated pulmonary manifestations (septic vasculitis, malignant melanoma, Kaposi sarcoma); (c) primary pulmonary diseases with associated cutaneous manifestations (tuberculosis, Pseudomonas pneumonia, mycoplasmal pneumonia, adenocarcinoma, metastasis); and (d) cutaneous-pulmonary conditions (multisystem disorders) (progressive systemic sclerosis, systemic lupus erythematosus, Wegener granulomatosis, sarcoidosis). A series of selected cases is used to illustrate the radiologic and dermatologic features of conditions that affect both the lung and dermal tissue. Specific emphasis is placed on the dermatologic manifestations of disease. Diagnosis of a pulmonary-cutaneous disorder requires familiarity with the morphologic appearance of the cutaneous lesion.
Adult↗
Dose-related opposite effects of hydrocortisone on hepatocyte proliferation in the rat.
To evaluate the role of glucocorticoids in the regulation of hepatocyte proliferation, high doses (6.25 mg/kg or more) and low doses (1.25 mg/kg or less) of hydrocortisone were injected into various categories of rats which had very different levels of proliferation. We used: (a) suckling rats whose stable unsynchronized proliferation can be stimulated and synchronized by acute inflammation or cyproterone feeding; (b) adult rats with a low level of proliferation, and (c) 2/3 hepatectomized rats during the first period of synchronized proliferation or during the second period of lower and unsynchronized proliferation. The kinetics of the labelling index and mitotic index were observed after hydrocortisone injection. High doses inhibited proliferation, as already found by many investigators. This effect was observed in suckling and hepatectomized rats and during acute inflammation in suckling or adult rats. Low doses had no inhibitory activities and, on the contrary, stimulated proliferation in some situations. The highest stimulations were observed during the early period after 2/3 hepatectomy or in combination with acute inflammation either in suckling rats or in 2/3 hepatectomized rats during the late period of regeneration. In all these situations hydrocortisone was a cofactor active during the early G1-phase. In contrast, in normal suckling rats a slight stimulation was observed due to an action at the G0-G1 transition. No such effect was found in adult rats. Our data show that doses of hydrocortisone in the therapeutic range or close to physiological values do not inhibit and, on the contrary, can stimulate hepatocyte proliferation.
Age Factors↗
Purification and partial characterization of a hepatocyte antiproliferative glycopeptide.
A low molecular weight compound, which inhibits the G1-S transition in rat hepatocytes, was obtained by tryptic hydrolysis of human alpha 2-macroglobulin followed by ultrafiltration at pH 10. It was purified by high-performance liquid chromatography on mu Bondapak C18 and mu Bondapak NH2 with a practically quantitative yield; from 5.1 g of alpha 2-macroglobulin, 2.8 micrograms of purified compound were recovered. Inactivation by specific enzymes and chemical analyses showed that the inhibitor is a sialylated glycopeptide whose peptide moiety contains a pyroglutamyl residue. Its molecular mass, estimated by gel permeation chromatography, would be in the interval 3,500-4,600. However, amino acid analyses indicated that it is not yet pure. All these data suggest that alpha 2-macroglobulin could be the carrier of the precursor form of the glycopeptide.
Amino Acids↗
[Stimulation, by acute inflammation, of the proliferation in preneoplastic hepatocyte foci expressing the gamma glutamyl transpeptidase, induced by diethylnitrosamine in adult rats].
Acute inflammation induces 20% of hepatocytes to initiate a mitotic cycle in 10 day-old rats but only 1% in adults. gamma GT-positive cell foci were induced by diethylnitrosamine in the liver of adult rats. Proliferation of gamma GT-positive hepatocytes was increased by the acute inflammation that followed a subcutaneous injection of an irritating substance, but proliferation in the surrounding liver tissue remained at the low control level. This difference of sensitivity to the mitogenic stimulation, which mimics the difference between the sensitivity of hepatocytes in suckling and adult rats, gives gamma GT-positive hepatocytes a proliferative advantage over normal cells. Acute inflammation may thus promote the evolution of preneoplastic foci and hepatoma formation.
Acute Disease↗
Inhibition of hepatocyte proliferation in vivo by a glycopeptide from rat serum.
The activity of a glycopeptide prepared from rat serum by treatment with trypsin and ultrafiltration was investigated in several in vivo proliferation systems. In baby rat hepatocytes synchronized by a subcutaneous injection of casein solution it caused a G1-S block, stopping cells at the end of the G1 phase and sending them back to the G0 phase. The glycopeptide also caused a G1-S block in young adult rats during the first semi-synchronized wave of proliferation that followed partial hepatectomy. Inhibition of hepatocyte proliferation by the glycopeptide was suppressed by blood proteins from normal rats but not from acute phase rats. Alpha 1-acid glycoprotein, an acute phase protein, increased this inhibition and reversed the antagonistic effect of normal blood proteins. In normal baby rats a G1-S block of non-synchronously proliferating hepatocytes was produced in two situations in which the antagonistic effect of normal blood proteins was eliminated: after treatment of the glycopeptide with leucine-aminopeptidase, and after mixing it with alpha 1-acid glycoprotein. The glycopeptide did not inhibit cell proliferation in kidney, submaxillary gland, or tongue epithelium. It seems to be the active component of a system that inhibits the proliferation of hepatocytes, probably by reducing their sensitivity to various mitogenic stimuli.
Animals↗
In vitro effect of a glycopeptide acting in vivo on hepatocyte cell cycle.
A factor specifically inhibiting the hepatocyte cell cycle in vivo was found to block the G1-S transition of liver cells in vitro. It proved to be non-toxic in our culture conditions, as judged by the reversibility of the effect on cell proliferation. It was not active on DNA synthesis in fibroblastic cell lines (3T3).
Animals↗
[Release from human alpha 2-macroglobulin of a peptide inhibitor of G1-S transition of hepatocytes in vivo. Role of trypsin, thrombin and various chemical agents].
Inhibitory effect on the G1-S transition of hepatocytes in vivo was measured in the ultrafiltrates of alpha 2 M/trypsin and alpha 2 M/thrombin complexes (alpha 2 macroglobulin: alpha 2 M). Untreated human alpha 2 M activity corresponds to one inhibitory unit/mg. When alpha 2 M/trypsin and alpha 2 M/thrombin complexes were ultrafiltrated at pH 7.8 on PM 10 Amicon membrane, 300 inhibitory units were obtained from 1 mg of alpha 2 M. After treatment at pH 10 of the same complexes, 30,000 inhibitory units were obtained from the same quantity of alpha 2 M. Such a high activity was observed when native alpha 2 M was used before alpha 2 M/enzyme interaction. When alpha 2 M was previously treated by an aliphatic amine or reduced and alkylated, the activity found in ultrafiltrates was very low. In the same way, a low activity was observed when the captation capacity of alpha 2 M was exceeded. These results show that specific cleavages on alpha 2 M molecule are needed to obtain a large amount of active inhibitory peptide.
Cell Cycle↗
[Detection and purification of a liver microsomal enzyme inducing the release of a glycopeptide inhibitor of hepatocyte proliferation from human alpha 2 macroglobulin].
The interaction rat liver microsomes/human alpha 2 macroglobulin releases in vivo an inhibitory peptide of the hepatocyte proliferation. Treatment of Triton X 100 on adult rat liver microsomes enables the solubilisation of a proteolytic enzyme. Its partial purification was obtained by Ultrogel AcA 44 filtration followed by a DEAE Sephacel chromatography. This enzyme shows a proteolytic activity in presence of calcium on synthetic substrates including Phe, Tyr and Trp. A whole enzyme inhibition is got after treatment by DFP or benzamidine. In presence of highly purified human alpha 2 macroglobulin this enzyme releases a glycopeptide of low molecular weight, which inhibits the hepatocyte proliferation during the G1-S transition in baby rat.
Animals↗