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Biomedical subjects

S Markowitz

Publications and source records attributed to S Markowitz.

At least 73 records · Page 4Linked to original sources
PubMed1988

Ergot alkaloids block neurogenic extravasation in dura mater: proposed action in vascular headaches.

Although the ergot alkaloids (ergots) are useful drugs for the acute treatment of migraine headaches, their mechanism of action remains obscure. When administered to rats in clinically relevant doses, ergots blocked the development of neurogenic plasma extravasation in dura mater. Plasma extravasation was induced by depolarization of perivascular axons following capsaicin injection or unilateral electrical stimulation of the trigeminal nerve. The ergot action could not be accounted for by vasoconstriction alone because neurogenic plasma leakage was not blocked by angiotensin or phenylephrine. Furthermore, ergots did not block plasma extravasation induced by administering sensory neuropeptides that mediate enhanced permeability. We propose that the therapeutic effects of ergots in vascular headaches may result from peripheral blockade of small fiber (C or A-delta)-dependent neurogenic inflammation within the dura mater.

Animals↗
PubMed1988

Neurogenically mediated plasma extravasation in dura mater: effect of ergot alkaloids. A possible mechanism of action in vascular headache.

C-fiber-dependent neurogenic plasma extravasation developed in the dura mater but not the brain after electric stimulation of the rat trigeminal ganglion or after chemical stimulation of perivascular axons with intravenous capsaicin, a drug that depolarizes sensory nerve fibers. C-fiber-independent extravasation also developed in this tissue after intravenous injections of substance P or neurokinin A (two constituents of unmyelinated C fibers) and after serotonin, bradykinin, or allergic challenge in presensitized animals. Intravenous dihydroergotamine or ergotamine tartrate, in doses similar to those used to treat migraine and cluster headache, prevented the stimulation-induced leakage of plasma proteins within the dura mater. Not unexpectedly, the acute administration of methysergide, a drug effective in the prophylactic treatment of headache, was inactive in this acute model. Neither acute nor chronic administration of propranolol affected stimulation-induced leakage of plasma protein. These results demonstrate that neurogenic inflammation develops within the dura mater in the rat and that ergot alkaloids prevent the process by a C-fiber-dependent mechanism.

Animals↗
PubMed1988

Transcriptional activation and DNase I hypersensitive sites are associated with selective expression of the gastrin-releasing peptide gene.

The gastrin-releasing peptide (GRP) is a neuropeptide hormone and growth factor produced normally by neural and neuroendocrine cells, as well as by human small-cell lung cancer (SCLC) tumors and derived cell lines. This study compares the structure of the human prepro-GRP gene in four SCLC cell lines that express variable levels of steady-state GRP mRNA. The regulation of GRP gene expression appears to be at the level of primary transcription based on nuclear run on studies. In the two SCLC cell lines expressing GRP we find a single transcription start site for GRP mRNA, and near this site we find four DNase I hypersensitive sites. These hypersensitive sites are absent in the two cell lines that do not express GRP. The presence of DNase hypersensitive sites in the promoter region of the GRP gene is the structural feature that best correlates with transcriptional activation. These four DNase hypersensitive sites are candidates for cis acting regulatory regions, which may be important in determining the level of transcription of the human prepro GRP gene.

Base Sequence↗
PubMed1987

The effect of mild hypoxemia maintained for twenty-four hours on maternal and fetal glucose, lactate, cortisol, and arginine vasopressin in pregnant sheep at 122 to 139 days' gestation.

The effects of prolonged mild hypoxemia on the fetus have received little attention. We investigated the response to a decrease in fetal arterial Po2 of 5 mm Hg or less sustained for a period of 24 hours in the chronically instrumented fetal lamb. Hypoxemia was induced by an infusion of nitrogen via the maternal trachea for 24 hours in 13 pregnant sheep at 122 to 139 days' gestation. Two control periods of air infusion via the maternal trachea for 24 hours were alternated with hypoxemia. Fetal hypoxemia was not associated with any change in fetal pH. During the first and second exposures to hypoxemia, there was an increase in fetal plasma lactate of 22.8 +/- 22.3 and 15.3 +/- 14.6 mg.dl-1 (mean +/- SD) above preliminary values (p less than 0.05) compared with the control period. Fetal plasma cortisol also increased by 5.7 +/- 6.1 and 9.5 +/- 5.4 ng.ml-1 (mean +/- SD) (p less than 0.05) compared with the control period. These results suggest that the fetal lamb at 122 to 139 days' gestation is highly sensitive to small decrements in Po2 of 5 mm Hg or less.

Animals↗
PubMed1987

Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain.

Utilizing 125I-BSA administered intravenously, a simple, reliable, and sensitive method was established for the detection of plasma protein extravasation in the dura of rats and guinea pigs following chemical, electrical, or immunological stimulation. Extravasated 125I-BSA or Evans blue was noted in the dura and conjunctiva but not in the temporalis muscle of saline-perfused rats following intravenous capsaicin, 1 mumol/kg. Capsaicin-induced extravasation was mediated by unmyelinated and small myelinated fibers since leakage did not develop in adult animals in whom these fibers were destroyed by capsaicin pretreatment (50 mg/kg) as neonates. An ipsilateral increase in Evans blue and 125I-BSA was found in the dura, eyelids, lips and gingival mucosa, and snout following electrical stimulation of the rat trigeminal ganglion. This increase was also C-fiber dependent. Among those peptides contained in perivascular afferent fibers and administered intravenously, substance P (SP) and neurokinin A (NKA), but not calcitonin gene-related peptide, caused a dose-dependent extravasation in the dura and conjunctiva of rats. Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva. Intravenous administration of 5-HT or bradykinin to normal adult rats or adult rats pretreated as neonates with capsaicin increased levels of 125I-BSA in both the dura and the conjunctiva. Histamine and prostaglandin E2, on the other hand, caused protein leakage in the conjunctiva but not in the dura of rats; however, histamine did induce extravasation in the dura of guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Acute post-infection glomerulonephritis caused by new 'thongs'. A case report.

Acute glomerulonephritis complicated secondary infection in a patient suffering from traumatic blisters caused by new footwear. This unlikely setting for acute glomerulonephritis was made more interesting by its occurrence in an adult in contrast with its more frequent recognition in a child. The age of the patient and the severity of the local symptoms masked the significance of the initial finding of haematuria until deteriorating renal function indicated the diagnosis of concomitant glomerular disease.

Acute Disease↗
PubMed1986

Human papillomavirus infection related to oesophageal carcinoma in black South Africans. A preliminary study.

Oesophageal specimens derived from 70 patients with established invasive squamous cell carcinoma of the oesophagus were histologically reviewed with special reference to the morphological manifestations of human papillomavirus (HPV) infection. Epithelial changes fulfilling the criteria for HPV infection were noted in 23 cases (33%). The presence of HPV antigens was demonstrated by immunohistochemical staining in 7 of these 23 cases. Although acceptable for routine diagnostic purposes, histological typing and immunoperoxidase staining methods are not entirely conclusive of HPV infection. Electron microscopy for detection of viral particles and a molecular hybridization technique have to be used for absolute confirmation and viral subtyping. The results of this pilot study will be used for prospective studies to determine the role of HPV infection in the aetiology of oesophageal carcinoma.

Adult↗
PubMed1986

Renal adenocarcinoma presenting with bilateral metastases to Bartholin's glands: primary diagnosis by aspiration cytology.

The first recorded case of renal adenocarcinoma presenting with bilateral metastases to the Bartholin's glands is presented. Primary diagnosis of the metastatic deposits was made by fine-needle aspiration cytology with subsequent localization of the unsuspected renal primary. The value of fine-needle aspiration in the identification of inapparent primary tumors is discussed and cytological findings are described in detail.

Bartholin's Glands↗
PubMed1986

Effect of posture on vital capacity.

The influence of some extreme body postures on vital capacity (VC) was examined in young adult humans. Two postures required full support of body weight by the arms: arms up, hanging from a bar, and arms down with hands gripping parallel bars. Three involved muscles that flex and extend the trunk: a partial sit-up position while supine and nearly maximal spinal extension and flexion while standing. Changes at the inspiratory and expiratory volume extremes were recognized by having the subjects do two VC efforts: the first standing and the second in the posture in question while continuing to breathe on the spirometer. Control observations in which the second of a VC pair was performed in an unstressed posture allowed correction for the influence of rebreathing. The changes in corrected VC were small, the greatest being an average reduction of approximately 8% in the partial sit-up position. During full support of body weight by the arms, the VC was slightly increased due to a significant increase in the inspiratory extreme and no change in the expiratory extreme. Spinal extension produced small increases in lung volume at both extremes with no significant change in VC, whereas spinal flexion did not influence the upper extreme but did increase lung volume at the lower extreme. The changes are discussed in terms of trunk muscle action.

Adolescent↗
PubMed1983

Timolol: a 4-year follow-up study.

In 25 patients with ocular hypertension and open angles timolol maleate lowered the intraocular pressure (IOP) of 71% of the 49 eyes treated, keeping it below 22 mm Hg during 4 years of therapy. However, the IOP tended to drift upward by 2 to 4 mm Hg per year, especially during the first and third follow-up periods (1 year and 2 years long respectively). Thus, patients should be examined every 3 months after an adequate response to therapy is achieved. In this series of patients there was a slight visual loss in about 38% of patients, but it was probably related to increasing age. Field loss occurred in four patients in spite of a good response to therapy. Increased cupping of the optic disc occurred in six patients, four of whom had had a pretreatment IOP of 30 mm Hg or greater. Timolol therapy was well tolerated by the patients, being virtually symptom-free. However, special care would be needed in treating patients with asthma, bradycardia or congestive heart failure.

Adult↗
PubMed1981

The carboxyl-terminal domain of human erythrocyte band 3. Description, isolation, and location in the bilayer.

Band 3, the anion channel protein of the human erythrocyte, is the major transmembrane glycoprotein of the erythrocyte membrane. The protein is distributed in a broad 88,000-98,000-dalton band on gel electrophoresis. Previous investigations have defined an NH2-terminal cytoplasmic domain and an adjacent membrane-spanning domain of the Band 3 molecule. The fragments containing these domains appear as discrete bands by sodium dodecyl sulfate polyacrylamide gel electrophoresis. A carboxyl-terminal fragment of the Band 3 molecule was generated by digestion with chymotrypsin at the external face of intact erythrocytes. This fragment appears as a broad band of Mr = 34,000-45,000. It has a site accessible to lactoperoxidase at the internal face of the membrane and must, therefore, span the membrane. Slices from different regions of the broad electrophoretic band of the carboxyl-terminal fragment of Band 3 all have identical peptide maps. The same is true of Band 3. Therefore, despite their heterogeneous appearance on gels, Band 3 and its proteolytic fragments are homogeneous polypeptides. This conclusion is supported by the finding of an unique NH2-terminal tetrapeptide sequence for one Band 3 fragment. The apparent heterogeneity of Band 3 and its carboxyl-terminal region may reflect variability of glycosylation or sodium dodecyl sulfate binding.

Affinity Labels↗
PubMed1981

Enhancement and inhibition of phagocytic activity in the retinal pigment epithelium.

The phagocytic activity of the pigmented epithelium of the bovine retina was studied with an organ culture model. Latex particles coated with immunoglobulin, or bovine rod outer segments, both labelled with radioactive iodine, were the objects to be phagocytosed. Various agents were tested with this model for their effects on phagocytosis by the retinal pigment epithelium. Iodoacetate significantly inhibited phagocytosis, as did penicillin, though to a lesser extent. Concanavalin A and gentamicin enhanced phagocytosis. Dimethyl sulfoxide had no effect. The results with lymphokines were not conclusive.

Animals↗
PubMed1980

Substance P increases hypothalamic blood flow via an indirect adrenergic-cholinergic interaction.

1 Hypothalamic blood flow (HBF) was measured in conscious rabbits by the 133xenon washout technique. 2 Substance P in a dose of 50 or 500 ng increases HBF while 5 ng is without effect. 3 Cholinoceptor blockade, with either atropine or mecamylamine abolishes the vasodilator effect of substance P. 4 Chemical sympathectomy of the hypothalamus with 6-hydroxydopamine, or adrenoceptor blockade with either propranolol or phenoxybenzamine abolishes the effect of substance P on HBF. 5 Destruction of the intracerebral noradrenergic pathway (INP), or blockade of its vasodilator action, with barbiturate or bicarbonate, likewise prevent the vasodilator action of substance P. 6 These results suggest that substance P may cause an increase in HBF via the release of endogenous acetylcholine, which in turn stimulates the INP.

Acetylcholine↗