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Biomedical subjects

M Hirsch

Publications and source records attributed to M Hirsch.

At least 19 recordsLinked to original sources

Lectin-binding sites in quick-frozen, freeze-substituted extracellular matrix of rabbit corneal stroma: a comparative electron microscopic study with different embedding procedures.

The efficiency of Epon, Lowicryl K4M and LR White resins for electron microscopy was tested on the reactivity of carbohydrate residues to lectins in quick-frozen, freeze-substituted extracellular matrix of rabbit corneal stroma, without the use of any chemical fixation. Three lectins conjugated to gold particles were used in a post-embedding method: Wheat germ agglutinin, Concanavalin A and Ricinus communis agglutinin 1. Best gold-labelling was obtained with Lowicryl K4M for Wheat germ agglutinin, and with both Lowicryl K4M and Epon for Concanavalin A and Ricinus communis agglutinin 1. Tissues embedded in LR White gave less intense labelling for the three lectins used in comparison with the two other resins. This study demonstrates the crucial role of resins in the optimal preservation of biological activity of carbohydrate residues in cryotechnically-processed cornea for electron microscopy.

Animals

Changes in cellular membrane and paracellular conductances by amphotericin B in the epithelium of the bullfrog cornea.

In the isolated bullfrog cornea, measurements of DC electrical parameters in conjunction with AC impedance and ultrastructural analyses were used to determine the effects of 10(-5) M amphotericin B on epithelial cellular membrane and paracellular conductances. In NaCl Ringers, amphotericin B elicited a 3.5-fold increase in the specific apical membrane conductance (Ga/Ca); where Ga and Ca are the apical membrane conductance and capacitance, respectively. The basolateral membrane conductance (Gb) and the basolateral membrane capacitance (Cb) fell by 57% and 50%, respectively. In the paracellular pathway, the tight junctional complex (Gj) was unchanged whereas the lateral intercellular space resistance (Rp) decreased by 55%. The declines in Gb and Cb were suggestive of cell volume shrinkage because these changes were consistent with a previously described decline in intracellular K+ content and reduction in exposed basolateral membrane area to current flow. Ultrastructural analysis validated that amphotericin B caused cell volume shrinkage because there was: (1) increased folding of the basolateral membrane and waviness of the basal aspects- of the plasma membrane; (2) dilatation of the lateral intercellular spaces. This agreement suggests that intracellular activity decreased following exposure to amphotericin B which resulted in cell volume shrinkage and an impairment of Cl- uptake across the basolateral membrane.

Amphotericin B

New method of ultrastructural localization of WGA-binding sites in the rabbit cornea using quick-frozen specimens followed by freeze-substitution.

Wheat germ agglutinin (WGA) conjugated with apo-horseradish peroxidase-gold was used as a probe for ultrastructural localization of N-acetyl-glucosamine and N-acetyl-neuraminic acid residues of glycoconjugates in posterior stroma and Descemet's membrane of rabbit corneas. Ultra-thin sections of quick-frozen, freeze-substituted, and Epon or Lowicryl K4M-embedded tissue were used. Numerous WGA-binding sites were detected in the stromal matrix and Descemet's membrane in both embedding procedures. Labelling was more intense with low-temperature embedding in Lowicryl K4M than with Epon. Gold particles preferentially labelled the major collagen fibrils of the stroma but otherwise appeared uniformly distributed over both extracellular matrices, except in some areas of the stromal matrix that were barely labelled. Frequently, the inter-particle distance of gold particles on collagen fibrils corresponded to the banding period of type I collagen fibrils, suggesting that they point out keratan sulphate proteoglycans which contain WGA-binding sites. The combination of cryotechniques and post-embedding procedures may be very effective for lectin histochemistry of the cornea and other eye tissues.

Acetylglucosamine

Traumatic atlanto-occipital dislocation in children: review and report of five cases.

Traumatic atlanto-occipital dislocation has usually been considered incompatible with life. However, reports on survivors stress the need for early clinical diagnosis of this condition, particularly in the context of multiple trauma, in order to avoid life-threatening diagnostic manipulations and to provide adequate treatment. Five instances of atlanto-occipital dislocation in children observed during the last two years prompted this report, since four of them survived only temporarily. The radiologic and computed tomographic (CT) findings have been reevaluated. Use of metrizamide CT is advised in clinically suspected cases with inconclusive radiologic workup.

Atlanto-Occipital Joint

Transvaginal sonography in postmenopausal women.

Transvaginal sonography (TVS) is a recent addition to the diagnostic techniques available for the evaluation of the female pelvis. Our experience in over 200 cases of postmenopausal women is the subject of this synoptic review. Using this technique in 60 women, we were able to detect endometrial changes such as endometrial carcinoma or adenomatous hyperplasia in 81% and in a group of 19 patients myometrial invasion in 84%. Fibroids of different sizes and locations could be recognized, some of them with signs of cystic degenerations. In 48 postmenopausal women, TVS was used to follow the morphologic changes in the endometrium stimulated by hormone replacement therapy. Histological features of the endometrium were in close correlation with the sonographic patterns obtained. Ultrasound evaluation has been suggested as a possible screening tool for early changes in ovarian size and morphology. Fifty patients were evaluated for the effectiveness of TVS to detect ovarian pathology. The sensitivity and specificity were 83% and 100%, the same as that of gross examination of the ovary at the time of surgery. It seems that TVS is a reliable tool in the detection of early changes in the postmenopausal ovary, but further evaluation in a large population is necessary to assess the usefulness of TVS as a routine screening tool for early ovarian carcinoma. Twenty-nine postmenopausal women with unilateral simple cysts (diameter less than or equal to 5 cm) were identified. All exhibited benign histopathologic changes. We conclude that small (less than 5 cm) postmenopausal cysts have a low incidence of malignancy and could be followed by TVS without immediate surgical intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Congenital hereditary hypothyroidism--prenatal diagnosis and treatment.

Intrauterine diagnosis of congenital hypothyroidism was established on the basis of TSH concentration in amniotic fluid in the 22nd week of gestation for the offspring of a couple both known to have an iodide organification defect. Prenatal treatment consisted of intramniotic injections of 500 mcg Na-1-thyroxine, which was administered from the first amniocentesis until one week before delivery. Following delivery, the diagnosis was confirmed by the elevated level of TSH, 60.5 uU/ml, and a gradual decrease of fT4 to 0.8 ng/ml. Regular substitution therapy was commenced on the third day of life. The normal shape and location of the thyroid gland was demonstrated by Technetium scintiscan. At 18 months the infant revealed no significant deviation from normalcy in growth or mental capacity. This experience indicates that testing of amniotic fluid for TSH in the 22nd week of gestation can be diagnostic for congenital primary hypothyroidism. Furthermore, it is suggested that the treatment approach described is warranted in all cases in which there is a high risk of congenital primary hypothyroidism.

Amniotic Fluid

Pulmonary plasma-cell granuloma.

A large pulmonary plasma-cell granuloma (PCG) mimicking a mediastinal germinal-cell tumor in a 9-year-old boy is presented. The nonspecificity of the tumoral calcifications and of the radiographic and CT findings in pulmonary PCG is demonstrated.

Calcinosis

[The of effect of rolitetracycline on oxygen consumption in a suspension of E. coli].

Authors studied the oxygen demand by E. coli suspensions (serotypes 023 and 026) modifying it with various concentration of Rolitetracyclin, and proceeded by comparison of both serotypes. Time dependence of oxygen demand has been determined using the direct Warburg's manometric method. The obtained results are summerized as following four points: 1. Tested Rolitetracyclin doses caused the decrease in oxygen demand of E. coli suspensions significantly for the majority of time intervals. Rolitetracyclin actioned similarly in both serotypes. 2. Rolitetracyclin 0.5 microgram concentration actioned bacteriostatically on both serotypes, and showed more pronounced action on E. coli 026 serotypes with higher metabolic activity. 3. Rolitetracyclin 5 and 50 micrograms bactericidal concentrations inhibited markedly the oxygen demand in both serotypes. 4. Using this method allowed to determine the difference in metabolic activity of both E. coli serotypes tested.

Escherichia coli

[Angiographic management of angiomatous malformations in the central nervous system].

Angiomatous malformations of the central nervous system are relatively rare and have a serious prognosis. Clinical manifestations of such lesions of the spine include back pain associated with motor and sensory weakness, progressing to complete paraplegia. In angiomatous involvement of the brain, the symptoms may progress from headaches to coma and death. Computerized tomography and magnetic resonance imaging are new noninvasive modalities used in the diagnosis of such malformation, but they have not replaced myelography and angiography. Up to the past decade, the management of angiomatous lesions of the CNS was only surgical. Angiographic embolization is now widely accepted as an alternate method of management. Experience with embolic treatment of 3 cases is reported. In a 15-year-old boy with two adjacent thoracic vertebral hemangiomas (D7 and D8) compressing the spinal cord, embolization was used before surgery. A 23-year-old man with acute myelopathy due to extraretro-medullary arteriovenous malformations of the spinal cord (D9-D11) was successfully treated by selective embolization via catheter of the right 10th intercostal feeding vessel. An 82-year-old man had proptosis, bruit and pulsation in the right eyeball and loss of vision. Arteriovenous malformation of the dura of the anterior cranial fossa was demonstrated and was completely cured by bilateral selective embolization of the feeding branches of the internal maxillary arteries.

Adolescent

Circulating p24 antigen levels and responses to dideoxycytidine in human immunodeficiency virus (HIV) infections. A phase I and II study.

STUDY OBJECTIVE: To determine the safety and efficacy of dideoxycytidine in patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex. DESIGN: A partially randomized phase I and II outpatient, dose-ranging study. SETTING: Four university medical centers involving government-supported referral AIDS Clinical Trial Units. PATIENTS: Sixty-one patients with AIDS or advanced AIDS-related complex and 100 pg/mL or more serum p24 antigen titers. INTERVENTIONS: Dideoxycytidine was administered orally at 0.06, 0.03, 0.01, or 0.005 mg/kg body weight every 4 hours for 3 to 6 months depending on tolerance and benefit. MEASUREMENTS AND MAIN RESULTS: In patients receiving 0.06 and 0.03 mg/kg, diffuse erythematous rash, fever, and aphthous stomatitis occurred in the first weeks of therapy, but resolved later. Hematopoietic suppression was rare. Peripheral sensory neuropathy occurred in patients receiving 0.06 mg/kg and 0.03 mg/kg and improved after discontinuation of therapy. Serum p24 antigen fell significantly (P less than 0.01) from baseline entry values in most of these patients. The CD4 lymphocytes rose transiently at the 0.03 mg/kg dosage. At the 0.005 mg/kg dosage, skin rash, fever, and aphthous stomatitis were mild or absent. Peripheral neuropathy, which occurred in all patients receiving 0.01 mg/kg was less severe than at higher dosages. At the 0.005 mg/kg dosage, peripheral neuropathy was occasionally seen. Significant suppression of serum p24 antigen was seen in most patients with AIDS-related complex receiving 0.01 mg/kg and less frequently in patients receiving 0.005 mg/kg. CONCLUSIONS: Less toxic regimens of dideoxycytidine merit clinical assessment for advanced anti-human immunodeficiency virus-1 (HIV) infection. Several studies alternating dideoxycytidine and zidovudine are in progress.

AIDS-Related Complex

Development of tight junctions in the human ciliary epithelium.

Using the freeze-fracture technique, the tight junctions of the human ciliary epithelium were studied from 8 to 24.5 weeks of gestation with regard to their ability to act as a barrier to tannic acid. Zonular tight junctions were present as early as the 8th week of gestation, even before the emergence of ciliary folds, and they constituted an effective barrier to tannic acid at all stages studied. In the earliest stages, intramembranous particles were observed on the crest of membrane elevations, at regions of the future tight junctions. Discontinuous and loose networks of tight junctional strands were also encountered, indicating the formation of tight junctions. After the 10th week of gestation, ciliary folds developed and the configuration of the tight junctional networks underwent important changes. The apico-basal thickness of the junction, the number of superimposed strands, and the number of anastomoses decreased, while the number of complex strands increased. At the same period, junctional elements tended to become arranged in parallel lines. Steps which may lead to the formation of the tight junctions and the possible significance of the morphological modifications are discussed.

Ciliary Body

Dehydroepiandrosterone-sulfate/cortisol ratio in panic disorder.

We hypothesized that the dehydroepiandrosterone-sulfate (DHEA-S)/cortisol ratio, which has been used as an index of adrenocortical function, would be altered in panic disorder patients and would change after treatment. We evaluated 10 male and 14 female outpatients meeting DSM-III-R criteria for panic disorder. Of these 24 subjects, 13 were treated with clonazepam, 8 were treated with alprazolam, and 3 were treated with placebo as part of a double-blind study. The DHEA-S/cortisol ratio values in the 24 patients with panic disorder (mean = 20.5, SD = 11.6) were significantly higher than those of a group of 60 normal controls (mean = 11.5, SD = 6.01) and were also significantly higher than those of a group of 22 depressed patients (mean = 10.6, SD = 6.33). Although there was no significant difference in the pretreatment DHEA-S/cortisol ratio values between male (mean = 23.6, SD = 11.8) and female (mean = 18.2, SD = 11.3) panic disorder patients, the effects of treatment on this ratio differed between the two sexes. In fact, in the female patients there was a significant decrease in the DHEA-S/cortisol ratio at the end of the study (mean = 15.1, SD = 7.9), while in the male patients there was no significant change in this ratio at the end of the study (mean = 30.2, SD = 21.4). No significant differences were noted between pretreatment and posttreatment DHEA-S/cortisol ratio values in patients treated with alprazolam (n = 8), in patients treated with clonazepam (n = 13), or in patients treated with placebo (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Filipin-induced deformations in plasma membranes of cultured bovine corneal endothelial cells with incomplete belts of tight junctions.

Complete belts of intact tight junctions are thought to act as barriers to the movement of cholesterol in the plane of the plasma membrane. As cholesterol can be revealed by filipin-induced membrane deformations on freeze-fracture images, we studied the distribution of these deformation in cultured bovine corneal endothelial cells with incomplete belts of tight junctions. While the extent of filipin-induced deformations differed between individual cells, there is a homogeneous distribution of filipin-induced deformations on both sides of the incomplete junctional belt of endothelial cells. Our results suggest that cultured endothelial cells do not polarize cholesterol, possibly because of the incomplete tight-junctional barrier.

Animals