Biomedical subjects
J Muller
Publications and source records attributed to J Muller.
A new enzyme immunoassay of microsomal rat liver epoxide hydrolase.
Antiserum against purified rat liver microsomal epoxide hydrolase was produced in the rabbit. We developed an enzyme-linked immunosorbent assay which is reliable with regard to its analytical criteria. The concentration of epoxide hydrolase was measured in liver microsomes of control rats and animals treated with F 1379 (250 mg/kg/day) for 5, 7, 14, and 21 days. This hypolipidemic drug was able to induce strong epoxide hydrolase activity and enhance protein concentration. The gradual increase in epoxide hydrolase concentration paralleled the increase of epoxide hydrolase activity, with stabilization occurring after the 14th until the 21st day of treatment.
Treatment of polyhydramnios with prostaglandin synthetase inhibitor (indomethacin).
Polyhydramnios, which is caused by an excess of amniotic fluid, was diagnosed uniformly in eight patients by ultrasound examination and clinical symptoms, namely, premature uterine contraction, abdominal pain, and respiratory discomfort that resulted from excessive pressure on the diaphragm. Fetal anomalies incompatible with extrauterine existence were excluded by serum alpha-fetoprotein levels, repeated sonography, amniocentesis, and chromosomal analyses. Patients were treated with 2.2 to 3.0 mg of indomethacin/kg body weight/day. The treatment was started at an average gestational age of 24 +/- 0.5 weeks and continued for 2 to 11 weeks. All patients had significant improvement with a simultaneous reduction in amniotic fluid volume, fundal height, and umbilical perimeter. All patients were delivered satisfactorily at an average of 39 weeks' gestation. The fetuses were within the normal body weight range of 2750 to 3600 gm and showed normal development during the neonatal period of 2 to 6 months. Before delivery without indomethacin, the polyhydramnios reformed. Adverse effects or intolerance to the drug was avoided by either a reduction in the dose or cessation of indomethacin therapy. Our studies suggest that indomethacin therapy is an effective way to manage pregnancy complicated by polyhydramnios.
Kinetic analysis of inhibition of human adrenal steroidogenesis by ketoconazole.
The kinetics of the inhibitory effects of the imidazole antimicrobial ketoconazole on the activities of the steroidogenic enzymes distal to cholesterol side-chain cleavage were studied in human adrenal microsomal and mitochondrial suspensions. Although ketoconazole was a competitive inhibitor of all five enzyme reactions, the effects on 17-hydroxylase, 17,20-desmolase, and 11-hydroxylase activities (Ki = 10(-8) M) were considerably greater than those on 21-hydroxylase and 3 beta-hydroxysteroid dehydrogenase/isomerase activities (Ki = 10(-4) M). These findings explain the clinical endocrine effects of ketoconazole in the usual therapeutic doses, which include inhibition of cortisol and androgen secretion, compensatory ACTH-mediated secretion of 17-desoxysteroids such as progesterone and aldosterone, and suppression of PRA.
[Krukenberg's tumor. Apropos of a case. Review of the literature].
A case is reported of krükenberg's tumor, this rare lesion characterized by the constant presence of typical signet ring cells being an ovarian metastasis from a general digestive cancer. The primary neoplasm is often overlooked while the ovarian tumor is already large and bilateral. In a pregnant patient with this lesion virilization of mother and child may occur, this endocrine activity being poorly documented and the subject of a literature review. The pathogenicity of this tumor is still unknown. Endocrine investigations should be enlarged in the fairly rare cases when diagnosis is suspected prior to ovarian excision. Treatment is currently surgical but survival is little improved. Other therapy is only poorly effective.
Production and certification of an enzyme reference material for gamma-glutamyltransferase (CRM 319). Part 1: Preparation and characterization.
We have produced a batch of lyophilized gamma-glutamyltransferase as enzyme reference material. The "light" enzyme form was purified from pig kidney to a relatively high specific activity (120 kU/g) and was essentially free of contaminating enzymes. The partly purified gamma-glutamyltransferase, lyophilized in a matrix containing bovine serum albumin (Fraction V, 60 g/L), yielded a batch of 4000 ampules and was stored at -20 degrees C. The vial-to-vial variability with respect to the catalytic concentration of the final product (CV 0.6%) and its stability (predicted loss of activity at -20 degrees C was less than 0.01% per year) were considered sufficient to allow the use of this preparation for a certification procedure. The behavior of the reference material in comparison with human serum samples was evaluated three ways: (a) by kinetic characteristics, (b) by the ratio of activities for duplicate determinations by different methods, and (c) by use of the reference material to convert values obtained by various methodologies to those by the IFCC proposed method. The material appeared to be commutable for the two methods studied. The difference in the ratios obtained for patients' samples and reference material was less than +/- 5%, and the recalculated values for patients' samples as determined with the reference material differed from values determined by the IFCC method by no more than 4.8%.
Production and certification of an enzyme reference material for gamma-glutamyltransferase (CRM 319). Part 2: Certification campaign.
We describe the process of certification for a gamma-glutamyltransferase reference material (CRM no. 319). Fifteen laboratories participated to this interlaboratory evaluation. All steps of the measurements were controlled in an effort to locate potential sources of variations. In particular, the exclusion of some data was strictly documented or justified by the non-observance of the IFCC method and (or) discrepancies in instrumentation, reconstitution of the lyophilized samples, or measurement technique. Inaccuracy in the reconstitution of the lyophilized material was +/- 0.68%, and the molar absorptivity of the 5-amino-2-nitrobenzoate reported by each laboratory was within +/- 2% limits of the value reported by the IFCC. Calculated from the sets of accepted results, the total CV among samples was 2.6% and the overall CV was 3.2%. Within-day and between-day CVs were 1.1% and 1.4%, respectively. The greatest variation for a single component was the between-laboratory variability (CV 3.1%); the within-laboratory CV, including the day effect, was 1.8%. Finally, the certified value for the catalytic concentration of this enzyme in the reconstituted lyophilized reference material was 86.8 U/L with an uncertainty of +/- 2.1 U/L (0.95 confidence interval). The uncertainty appeared to be compatible with the end-use of this reference material.
[Improvement in the prenatal etiologic diagnosis of severe 2d trimester oligo-amnios by intra-amniotic injection of physiologic solution].
In reference to 4 severe cases of oligo-amnios of the second trimester of pregnancy, the authors advocate a method in order to improve the pre-natal diagnosis by intra-amniotic injection of a normal saline solution. This method facilitates the morphological exploration of the fetus by sonogram and enables to obtain a fetal karyotype by umbilical or amniotic tap. The potential risk of this technique are described.
I.U. School of Medicine revives John Shaw Billings History of Medicine Society.
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[False aneurysm of the superior mesenteric artery complicating a pancreatic pseudocyst. Report of a case and review of the literature].
The authors report a case of a pancreatic pseudocyst complicated by a false aneurysm of the superior mesenteric artery. The diagnosis was made possible thanks to the evocative images of echography and C.T. scanning permitting to perform on time the arteriography. The surgical treatment consisted on the exclusion of the false aneurysm, which necessitated a distal bypass to revascularise the intestinal tract, and the drainage of the pseudocyst by a Roux-en-Y loop. A review of literature is made.
Juvenile Alzheimer's disease with cerebellar involvement.
We describe a sporadic case of Alzheimer's disease with cerebellar involvement in a man, who died at age 32 years after an illness lasting seven years, which was marked by progressive dementia and ataxia. The brain was quite atrophic and showed numerous senile plaques of all types and neurofibrillary tangles in the cerebral cortex with some involvement of the basal ganglia and diencephalon. There was cerebellocortical atrophy with numerous large, kurulike plaques. In addition, widespread severe congophilic angiopathy was noted.
[Endometrial carcinoma and their precursors].
Endometrial carcinoma is significantly linked to the excess of exogenous and endogenous estrogens, non-tempered by progesterone. It is the second cancer in women after breast cancer. It is still detected with difficulty at the pre-invasive stage. Evaluation of its histological grade during the diagnosis (aspiration, curettage) influences the treatment. Grade I (80 p. cent of the cases) includes common carcinomas and their mucinous variants, with malpighian metaplasia, cytologically benign. Grade II concerns poorly differentiated carcinomas. Grade III concerns adeno squamous, anaplastic, seropapillar and clear cells carcinomas. The invasive stage, established on the operative specimen, represent the main prognostic factor. The risks of recurrence or metastases are practically non-existent when the carcinoma is localized to the endometrium, very low if the carcinoma invades a few mm of the myometrium, moderate if the medial half is involved, much higher if the invasion exceeds half of the thickness of the myometrium and/or involves the cervix.
Primary lymphoma of the central nervous system: a clinicopathologic analysis of 26 cases.
We analyzed 26 cases of primary lymphoma of the central nervous system. There were 14 males and 12 females ranging in age from 5-76 years (median age 51 years, mean age 50.2 years). None had received organ transplantation or immunosuppressive therapy. The most common presenting symptoms were headache, mental changes, nausea, vomiting, and convulsions. The main neurological findings were hemiparesis, papilledema, visual field defects, and cranial nerve palsies. The most common finding in the cerebrospinal fluid (CSF) was high protein content; CSF cytology was positive in only one case. Computerized tomography was done in 14 cases; all showed a contrast-enhancing lesion. Angiography generally revealed an avascular mass. The most common location above tentorium was the frontal lobe; in four cases the tumor was infratentorial (cerebellum, 3 cases). In five cases there was diffuse involvement of the brain; all had severe dementia and diagnosis was not made until the autopsy. Histologically, the most common type was diffuse histiocytic or immunoblastic lymphoma according to Rappaport and the Working Formulation classification respectively. Radiation therapy alone in five patients gave a median survival of 17 months. Five patients received radiation and chemotherapy, and median survival was 16 months. Two patients developed ocular lymphoma 8 and 36 months later that was treated by radiation.
Sampling of gaseous pollutants on silica gel with 1400 mg tubes.
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Complete response to vasopressin requires epithelial organization in A6 cells in culture.
Arginine vasopressin (AVP) stimulates adenylate cyclase activity in A6 epithelia grown on filters but not in A6 epithelia grown on plastic culture dishes. When A6 cells are subcultured from culture dishes and seeded at high density on filters, stimulation of adenylate cyclase by AVP is not evident for approximately 3 days. Peak stimulation by AVP occurs between 5 and 10 days. The time course for development of responsiveness to AVP corresponds to the development of an ordered epithelium with polarized cells, tight junctions, and a high transepithelial resistance. A similar correlation is seen when mature filter-grown epithelia that respond to AVP are dissociated by chelation of calcium and subcultured as single cells onto another filter. Stimulation of adenylate cyclase is not evident until an epithelium with significant electrical resistance is reformed. Filters seeded at 1.6 X 10(6) cells/cm2 require 1-2 days to show AVP sensitivity and electrical resistance; filters seeded at 0.4 X 10(6) cells/cm2 require 4 days. Experiments to test the function of the subunits of adenylate cyclase with forskolin (catalytic subunit) and with cholera toxin (Ns, guanine nucleotide-binding subunit) indicate that they are functional during the entire time and that it is the receptor for AVP that is not functional until an ordered epithelium has been formed.
Time-dependent attenuation of water flow in antidiuretic hormone-treated toad bladder.
Toad urinary bladders were subjected to sequential 30-min stimulation with antidiuretic hormone (ADH) followed by 30-min hormone washout over 4 h in the absence of a transmural osmotic gradient. Immediately thereafter, during test stimulation with hormone in the presence of a transmural gradient, transbladder water flow was profoundly inhibited, but intra(luminal)membrane particle aggregates, presumed markers of luminal membrane water permeability, were as numerous as in fully responsive controls. The protocol followed was designed to eliminate any distorting effect of prior water flow on cytoplasmic organization and to equalize, for both experimental and control tissues, the time of aggregate presence in the luminal membrane during final test stimulation. On the assumption that cytoplasmically stored and/or newly synthesized aggregates would be unaffected by the protocol followed, these observations appear to be consistent with the view that bladder refractoriness to prolonged ADH treatment may involve regulation of tissue water permeability at a resistance distal to the luminal membrane.
Regulation of the activities of 17-hydroxylase and 17,20-desmolase in the human adrenal cortex: kinetic analysis and inhibition by endogenous steroids.
Kinetic analyses of 17-hydroxylase and 17,20-desmolase activities have been performed on human adrenal microsomes from 12 individuals, aged 1-60 yr. The median Michaelis constant of 17-hydroxylase for the substrate pregnenolone was 0.09 microM, and that of 17,20-desmolase for the substrate 17-hydroxypregnenolone was 0.12 microM. The median maximum velocity of 17-hydroxylase (0.25 nmol/mg X min) was significantly greater than that of the desmolase (0.13 nmol/mg X min). There was no significant correlation between the age of the adrenal donor and the Michaelis constant, but the maximum velocity for both activities in the single infant donor was lower than the values in older individuals. The inhibitory effects of various steroids on both enzyme activities also were studied. All steroids examined, except cortisol, competitively inhibited both enzymes. In each case the inhibition constant was higher for 17-hydroxylase than for 17,20-desmolase, indicating that C21 side-chain cleavage would be more sensitive to inhibition by endogenous steroids. The results, taken together with those of similar studies of 3 beta-hydroxysteroid dehydrogenase kinetics, are compatible with the suggestion that increased enzyme synthesis mediated by ACTH and differential inhibition by endogenous steroids may, in part, account for developmental changes in adrenal hormone secretion.
Contribution of radon and radon daughters to respiratory cancer.
This article reviews studies on the contribution of radon and radon daughters to respiratory cancer and proposes recommendations for further research, particularly a national radon survey. The steady-state outdoor radon concentration averages 200 pCi/m3, and indoor levels are about 4 times higher. The primary source of radon in homes is the underlying soil; entry depends on multiple variables and reduced ventilation for energy conservation increases indoor radon levels. Occupational exposures are expressed in units of radon daughter potential energy concentration or working level (WL). Cumulative exposure is the product of the working level and the time exposed. The unit for cumulative exposure is the working level month (WLM). The occupational standard for radon exposure is 4 WLM/year, and 2 WLM/year has been suggested as a guideline for remedial action in homes. Epidemiologic studies show that miners with cumulative radon daughter exposures somewhat below 100 WLM have excess lung cancer mortality. Some 3% to 8% of miners studied have developed lung cancer attributable to radon daughters. All of the underground mining studies show an increased risk of lung cancer with radon daughter exposure. All cell types of lung cancer increased with radon exposure. If radon and smoking act in a multiplicative manner, then the risk for smokers could be 10 times that for nonsmokers. The potential risk of lung cancer appears to be between 1 and 2 per 10,000/WLM, which yields a significant number of lung cancers as some 220 million persons in the United States are exposed on average to 10 to 20 WLM/lifetime.