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Biomedical subjects

M David

Publications and source records attributed to M David.

At least 73 records · Page 4Linked to original sources

Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6.

Human hepatocytes in primary culture were used as a model system to investigate the mechanism(s) involved in the induction of the acute-phase response in human liver. Hepatocytes were incubated with increasing amounts of recombinant human interleukin-1 beta, recombinant interleukin-6 and tumor necrosis factor-alpha. Synthesis of C-reactive protein was studied at the mRNA and protein levels. Only recombinant interleukin-6 was capable of inducing C-reactive protein-mRNA and C-reactive protein-protein synthesis. Also, fibrinogen and alpha-1-antitrypsin synthesis measured by immunoprecipitation with specific antisera increased in a dose-dependent, time-dependent manner, whereas albumin synthesis decreased to about 50% of controls. Maximal effects were observed at 100 to 300 units of recombinant interleukin-6/ml culture medium after 20 hr of incubation. Although the synthetic glucocorticoid dexamethasone slightly modulated the effect of recombinant interleukin-6, it was not an absolute requirement for the induction of acute-phase protein synthesis in human hepatocytes. In pulse-chase experiments it was shown that the time course of the disappearance of the acute-phase proteins from the cells and their appearance in the medium is not influenced by recombinant interleukin-6. This finding suggests that recombinant interleukin-6 exerts its regulatory effect on acute-phase protein synthesis at the pretranslational level.

Acute-Phase Proteins

State of leukocyte adhesiveness/aggregation in the peripheral blood of pemphigus and psoriatic patients.

The purpose of this study was to assess the role of leukocyte adherence in the pathogenesis of the psoriatic lesion. Use was made of the fact that psoriasis and pemphigus differ considerably as to the presence of leukocytes in the respective lesions: abundance in psoriasis, and absence in pemphigus. The state of leukocyte adhesiveness/aggregation (LAA) was determined in the peripheral blood of 56 patients with psoriasis and 31 patients with pemphigus. Both classes of patients were subdivided into two categories according to the severity of the disease. It was found that in both diseases elevated values of LAA were obtained in the severe cases, whereas the mild cases did not differ significantly from normal controls. Thus, in psoriasis mean LAA values of 9.5% +/- 8% were recorded in the severe patients and 5.5% +/- 4.2% in the mild cases (p = 0.01), while in pemphigus the values were 15% +/- 9.6% and 6.6% +/- 3.7% respectively (p = 0.03). It is concluded that LAA per se does not play a primary role in causing the psoriatic lesion.

Cell Adhesion

Metabolism of epirubicin to glucuronides: relationship to the pharmacodynamics of the drug.

In pharmacokinetic studies of epirubicin, we observed that its main metabolite, epirubicin glucuronide, presented a marked interpatient variation. It was even possible to separate the patients into two groups: those with a high epirubicin glucuronide:epirubicin plasma ratio and those with a low ratio, with few patients in between. We retrospectively analyzed the clinical files of 48 patients who had been subjected to a pharmacokinetic study of epirubicin. We observed that those with a low epirubicin glucuronide:epirubicin ratio had significantly lower plasma levels of fibrinogen and alpha 2-globulins, suggesting that a reduced glucuronidation of epirubicin could be associated with hepatocellular insufficiency. These patients also had significantly lower percentages of change in granulocytes after therapy and responded better to the course of treatment studied. We cannot presently propose a hypothesis to explain these observations.

Epirubicin

Prenatal treatment of congenital adrenal hyperplasia: report of a new case.

A mother at risk for 21-hydroxylase deficiency was treated with oral dexamethasone (0.5 mg 12 hourly) from early pregnancy, in an attempt to prevent in utero virilization in case of a female fetus. Fetal karyotype was 46,XX, and because of a possible intra HLA recombination, treatment was continued to term. The newborn had a modest virilization and hormonal studies confirmed the diagnosis of congenital adrenal hyperplasia (CAH). This observation and review of the literature suggest that efficient prenatal treatment of CAH requires a higher and more frequent dosage of dexamethasone.

Adrenal Hyperplasia, Congenital

Segmental neurofibromatosis.

Two patients had localized multiple cutaneous neurofibromas; one had bilateral involvement of the scalp and the other had true segmental neurofibromatosis. Other signs of neurofibromatosis were absent. Segmental neurofibromatosis may not be related to the generalized types of neurofibromatosis but may be a cutaneous hamartoma.

Aged

Conjunctival involvement in pemphigus vulgaris: a clinical, histopathological and immunofluorescence study.

Eleven patients with pemphigus vulgaris and with eye complaints had histopathological and direct immunofluorescence (DIF) studies on biopsies of their conjunctivae. In eight of the patients the ocular symptoms preceded the other manifestations of pemphigus. None of the 11 patients had any detectable conjunctival blisters or erosions. The conjunctivitis in three of the patients proved on histopathology and DIF to be a manifestation of pemphigus vulgaris. In the remaining patients, conjunctival hyperaemia with or without a mucoid discharge was observed, but there were no specific histopathological features, although one of them had a positive DIF.

Adult

The clinical and histopathological spectrum of IgA-pemphigus--report of two cases.

Two new cases of neutrophilic bullous disease exhibiting bound and circulating intercellular IgA in vivo in both direct and indirect immunofluorescence (IF), for which the term IgA-pemphigus was recently proposed, are presented. The first case showed a unique constellation of clinical and histopathological features not previously described for IgA-pemphigus, resembling both dermatitis herpetiformis and pemphigus, for which the designation IgA-herpetiform pemphigus seems most appropriate. The second case showed clinical and histopathological features mimicking subcorneal pustular dermatosis for which the previously used term IgA-pemphigus foliaceus seems most appropriate. The previously reported 11 cases showing similar direct IF findings, as well as our two patients, illustrate the main differences between IgA-pemphigus and classic forms of this condition: (a) different clinical manifestations with the absence of Nikolsky's sign; (b) scanty acantholysis; an abundance of neutrophils, with occasional neutrophilic spongiosis; (c) absence of C3 on direct IF; (d) the lower sensitivity of indirect IF and low levels of circulating antibodies; (e) the relatively benign course of the disease; (f) the apparent responsiveness to sulphones in many cases. It is suggested that IgA pemphigus should be considered as an entity separate from, but closely related to, classic pemphigus.

Diagnosis, Differential

Semicircular lipoatrophy--a pressure-induced lipoatrophy?

A case of semicircular lipoatrophy, a rare form of localized lipoatrophy, is described in a 33-year-old woman. No precipitating factors such as trauma could be elicited by questioning. However, the patient subsequently realized that she had unwittingly been subjected to repeated daily trauma as she pressed the affected thigh against the edge of the wash bowl while applying make-up. This case thus supports a possible mechanical basis for this rare entity, and demonstrates the importance of taking a careful history in the search for the possible occurrence of minor episodes of trauma in such cases.

Adipose Tissue

Familial pemphigus vulgaris.

Familial pemphigus vulgaris was found in a Jewish woman and her son who developed the disease within a period of 18 months from one another. HLA typing was performed in the mother and son as well as in the unaffected father and sister. Examination of the HLA antigens in this family indicates that there may be different variants of DR4, DQw3 and that one of them carried by the mother and son as part of the haplotype A30, B18, DR4, DQw3 is associated with pemphigus vulgaris. Our findings are in favor of the concept that particular polymorphic residues of class II major histocompatibility molecules are correlated with disease susceptibility.

Adult

Esophageal involvement in pemphigus vulgaris: report of two cases and review of the literature.

Two patients with esophageal involvement of pemphigus vulgaris are presented, who were diagnosed histopathologically and by direct immunofluorescence. In most dermatological textbooks the possibility of esophageal involvement is not mentioned. In the English medical literature 11 cases have been reported. It seems that if upper gastrointestinal endoscopy had been done on a routine basis it might have shown that esophageal involvement is more widespread than present findings indicate.

Aged

Effect of etretinate on peripheral T lymphocytes in psoriatic patients before, during and after 6 months of therapy.

Total peripheral T lymphocytes, OKT4 helper/inducer cells and OKT8 suppressor/cytotoxic cells, as well as T lymphocyte function determined by the local xenogeneic graft-versus-host reaction (GVHR), were investigated in 14 psoriatic patients prior to institution of treatment with etretinate, during the course of treatment and 6 months after its initiation. After approximately 2 months of treatment, there was a significant increase in the number of E-rosette-forming lymphocytes and OKT4 subpopulations with a return to normal levels after 6 months of treatment. The GVHR was positive in only 5/11 patients prior to therapy but in 9/11 patients after 2 and 6 months. Our results indicate that etretinate has a stimulatory effect on T lymphocytes and their subset counts.

Adult

Simultaneous synthesis and degradation of rat liver glycogen. An in vivo nuclear magnetic resonance spectroscopic study.

Using 13C nuclear magnetic resonance spectroscopic methods we examined in vivo the synthesis of liver glycogen during the infusion of D-[1-13C]glucose and the turnover of labeled glycogen during subsequent infusion of D-[1-13C]glucose. In fasted rats the processes of glycogen synthesis and degradation were observed to occur simultaneously with the rate of synthesis much greater than degradation leading to net glycogen synthesis. In fed rats, incorporation of infused D-[1-13C]glucose occurred briskly; however, over 2 h there was no net glycogen accumulated. Degradation of labeled glycogen was greater in the fed versus the fasted rats (P less than 0.001), and the lack of net glycogen synthesis in fed rats was due to degradation and synthesis occurring at similar rates throughout the infusion period. There was no indication that suppression of phosphorylase a or subsequent activation of glycogen synthase was involved in modulation of the flux of tracer into liver glycogen. We conclude that in both fed and fasted rats, glycogen synthase and phosphorylase are active simultaneously and the levels of liver glycogen reached during refeeding are determined by the balance between ongoing synthetic and degradative processes.

Animals

[Ischemic vascular complications following thrombopenia induced by heparin. Diagnostic and therapeutic problems].

The authors report 21 cases of heparin-induced thrombocytopenia with ischemic vascular complications. The clinical presentations were peripheral arterial ischemia (16 cases), hemiplegia (1 case) and deep vein thrombosis (4 cases). The vascular surgeon confronted by these complications in an emergency situation should recognise the difficulties of clinical diagnosis (atypical forms) and biological investigations (problems of tests of platelet aggregation). Arterial occlusions are usually accessible to disobliteration with a Fogarty catheter without peroperative heparinisation. Delayed diagnosis explains the seriousness of these complications; in our series of 21 patients, there were 2 deaths, 1 paraplegia, 4 amputations due to arterial problems, 4 severe post-deep vein thrombosis conditions, two of which followed trans-metatarsal amputation. The diagnosis of heparin-induced thrombocytopenia implies immediate withdrawal of heparin therapy. A relay with a low molecular weight heparin is not without risk and should only be undertaken after a negative platelet aggregation test (with the low molecular weight heparin). These tests are rarely practicable in emergency situations and a relay using oral anti-vitamin K antagonists with a rapid onset of action is probably the safest option.

Adult