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Biomedical subjects

S Nag

Publications and source records attributed to S Nag.

At least 145 records · Page 8Linked to original sources

Ultrastructural localization of monosaccharide residues on cerebral endothelium.

Biotinylated lectins were used to localize oligosaccharides on the luminal plasma membrane of endothelium of intracerebral cortical vessels. Binding of concanavalin A, wheat germ and Ricinus communis-I was observed on the endothelial luminal plasma membrane of cerebral arterioles and capillaries indicating the presence of alpha-D-mannosyl, alpha-D-glucosyl, beta-N-acetylglucosaminyl, sialyl, and beta-D-galactosyl residues. Lectin binding occurred on the plasma membrane of pinocytotic vesicles open to the vascular lumen and on membranes at the luminal end of interendothelial junctions but not on membranes within junctions. Higher concentrations of Ulex europaeus-I, soybean, and Dolichos biflorus agglutinins were required to demonstrate the alpha-L-fucosyl and alpha-N-acetyl-D-galactosaminyl residues. Pretreatment of brain slices with neuraminidase accentuated the staining produced by soybean agglutinin and resulted in exposure of peanut agglutinin-binding sites on endothelium of arterioles and capillaries. In this respect cerebral endothelium differs from noncerebral endothelium which binds peanut agglutinin without prior neuraminidase pretreatment. The role of these saccharide residues in endothelial permeability and charge remains to be determined.

Animals↗

Interstitial radiation implantation for unresectable nonoat cell carcinoma of the lung. Techniques and preliminary results.

The majority of lung cancers are unresectable at diagnosis. The radiation tolerance of the surrounding spinal cord and heart limits the external radiation therapy dose. Interstitial radiation implantation was utilized to deliver higher radiation dose, sparing the surrounding normal tissues in patients with unresectable nonoat cell cancers of the lung less than 8 cm in diameter localized to the thorax with no associated pleural effusion. The methods of implantation included permanent interstitial iodine-125 implantation of the gross disease in the lung and/or lymph nodes delivering about 120 Gy (12,000 rads) in 1 year and removable iridium-192 interstitial implantation of residual disease in the mediastinum, chest wall, or margin or resection in the lung, delivering about 30 Gy (3000 rads) in three days. Supplementary external radiation therapy of 40 Gy (4000 rads) in 4 weeks is delivered 4-6 weeks after implantation. The interstitial implant procedure adds only about 45 minutes to 1 hour to the operating time, and converts a palliative procedure into a potentially curative treatment. This article presents our experience with 11 cases, with early short-term follow-up results, and is designed to stimulate others to evaluate a similar approach to improve local control and survival in unresectable lung cancers.

Adenocarcinoma↗

Polyneuropathy with vagus and phrenic nerve involvement in breast cancer. Report of a case with spontaneous remission.

Dysphagia, respiratory insufficiency, and bilateral vocal cord paralysis developed in a 70-year-old woman seven years after resection of a breast carcinoma. There was spontaneous partial remission of symptoms before death, in the absence of treatment. Necropsy showed both inflammatory and metastatic infiltrates of vagus nerves, with demyelination out of proportion to axonal loss. Spontaneous resolution of metastases-evoked inflammation within vagus and phrenic nerves may have been the basis of clinical remission.

Aged↗

Cerebral endothelial surface charge in hypertension.

Anionic groups on cerebral arteriolar endothelium were localized using cationized ferritin (CF), and alterations in the distribution of these groups were documented in arterioles with increased permeability to horseradish peroxidase (HRP) in angiotensin-induced acute hypertension. Normotensive animals showed a uniform distribution of anionic groups on the endothelial luminal plasma membrane when fixed or live vessels were reacted with CF. Anionic groups were localized at the mouth of pinocytotic vesicles in both preparations; however, only live cells demonstrated CF particles within vesicles, and the possibility that these represent pinocytosed CF particles cannot be ruled out. Cationized ferritin particles were not observed on the plasma membranes within interendothelial spaces in either of the preparations. Sixty percent of hypertensive animals with pressures over 200 mmHg showed increased arteriolar permeability to HRP. At 2.5 min, permeable arteriolar segments with active vesicular transport of HRP showed marked reduction or loss of CF binding. Capillaries and venules in the adjacent cortex and nonpermeable arterioles demonstrated linear endothelial CF binding similar to controls. Most permeable vessels of animals killed 6-20 min after onset of acute hypertension when the blood-brain barrier is usually closed showed CF binding on endothelium indicating that there is rapid restoration of the net negative charge. These studies demonstrate that increased arteriolar permeability in acute hypertension is associated with a transient alteration of surface charge. The mechanism by which charge is altered remains to be determined.

Angiotensin Amide↗

Cerebral changes in chronic hypertension: combined permeability and immunohistochemical studies.

Focal areas of recent and old necrosis are a consistent finding in brain in chronic hypertension. The possibility that areas represent foci of increased vascular permeability leading to chronic edema and tissue breakdown was investigated in the present study. Rats with chronic renal hypertension demonstrated increased cerebrovascular permeability in focal cortical areas throughout the 7-week period of study. Combined use of tracers and immunohistochemistry demonstrated that these areas of increased permeability with protein extravasation were of different ages. Stage I lesions showed protein in and around arteriolar walls with no cellular reaction indicating that these were very early lesions and corresponded to the findings using HRP as a tracer. Necrosis of the neuropil and an astrocytic and microglial response associated with diffuse collections of protein in the neuropil characterized stage II lesions. Stage III lesions consisted of glial scars or cystic spaces lined by astroglia and associated with absent or sparse protein deposits. Animals that died or were sick prior to killing and had diffuse cerebral edema showed large stage II cortical lesions associated with widespread serum protein extravasation into the white matter of both hemispheres. The principal mechanism resulting in the permeability alterations was enhanced pinocytotic transport of tracer across the endothelium of penetrating cortical arterioles. Vascular occlusion by thrombi was not observed in pial or intracerebral vessels. Our findings are consistent with the hypothesis that increased vascular permeability leads to chronic edema and tissue necrosis in chronic hypertension.

Animals↗

Enhancement of high intensity Iodine-125 brachytherapy by cis-platinum in a murine bladder tumor model.

The interaction of cis-platinum chemotherapy and high-intensity Iodine-125 brachytherapy was studied in C3H/He mice with MBT-2 tumors growing in the thigh. Brachytherapy was delivered by 3 Iodine-125 seeds of 10 mCi each implanted into the tumor. Ninety-six animals were randomly divided into 8 groups of 12 animals each. Each group was given either no treatment (control), cis-platinum alone or brachytherapy of 20, 40 or 50 Gy either alone or combined with cis-platinum. Cis-platinum 3 mg. per kg. was given every 5 days for 3 doses. The addition of cis-platinum enhanced the effects of Iodine-125 brachytherapy as shown by the end-points of tumor regrowth delay, local tumor control and median survival times. The sensitization enhancement ratio ranged from 1.2 to 1.9. Further experiments are to be conducted to study the normal tissue effect, therapeutic gain factor, effects of altering the time of administration of cis-platinum and the clinical use of high-intensity Iodine-125 for removable brachytherapy.

Animals↗

Pharmacological modification of blood-brain barrier permeability following a cold lesion.

The effect of desipramine, imidazole, thioridazine and trifluoperazine on blood-brain barrier (BBB) permeability after a 24 hour cold lesion was studied in rats. Changes in BBB permeability were determined using a quantitative horseradish peroxidase (HRP) assay. The four drugs tested did not alter the quantity of HRP in the cortex of control animals, or in the contralateral cortex of test animals. However, imidazole, desipramine and trifluoperazine significantly reduced the HRP extravasation in and around the cold lesion. Several mechanisms for this effect are suggested; one possible mechanism common to all these drugs is the reduction of increased vesicular transport in cortical vessels adjacent to the cold lesions.

Animals↗

Biliary tract neoplasms: a simple management technique.

This paper presents a simple, fast, and accurate afterloading method of delivering high radiation dose to tumors of the biliary tract, using radioactive iridium through a biliary drainage catheter. A Tuohy Borst sidearm adaptor permits concurrent drainage. The dose delivered in this manner can be used to supplement the palliative external beam radiotherapy, with minimal side effect.

Adult↗

Dependence on Ca2+ and tropomyosin of the actin-activated ATPase activity of phosphorylated gizzard myosin in the presence of low concentrations of Mg2+.

Ca2+ and tropomyosin are required for activation of ATPase activity of phosphorylated gizzard myosin by gizzard actin at less than 1 mM Mg2+, relatively low Ca2+ concentrations (1 microM), producing half-maximal activation. At higher concentrations, Mg2+ will replace Ca2+, 4 mM Mg2+ increasing activity to the same extent as does Ca2+ and abolishing the Ca2+ dependence. Above about 1 mM Mg2+, tropomyosin is no longer required for activation by actin, activity being dependent on Ca2+ between 1 and 4 mM Mg2+, but independent of [Ca2+] above 4 mM Mg2+. Phosphorylation of the 20,000-Da light chain of gizzard myosin is required for activation of ATPase activity by actin from chicken gizzard or rabbit skeletal muscle at all concentrations of Mg2+ employed. The effect of adding or removing Ca2+ is fully reversible and cannot be attributed either to irreversible inactivation of actin or myosin or to dephosphorylation. After preincubating in the absence of Ca2+, activity is restored either by adding micromolar concentrations of this cation or by raising the concentration of Mg2+ to 8 mM. Similarly, the inhibition found in the absence of tropomyosin is fully reversed by subsequent addition of this protein. Replacing gizzard actin with skeletal actin alters the pattern of activation by Ca2+ at concentrations of Mg2+ less than 1 mM. Full activation is obtained with or without Ca2+ in the presence of tropomyosin, while in its absence Ca2+ is required but produces only partial activation. Without tropomyosin, the range of Mg2+ concentrations over which activity is Ca2+-dependent is restricted to lower values with skeletal than with gizzard actin. The activity of skeletal muscle myosin is activated by the gizzard actin-tropomyosin complex without Ca2+, although Ca2+ slightly increases activity. The Ca2+ sensitivity of reconstituted gizzard actomyosin is partially retained by hybrid actomyosin containing gizzard myosin and skeletal actin, but less Ca2+ dependence is retained in the hybrid containing skeletal myosin and gizzard actin.

Actins↗

Paraneoplastic subacute necrotic myelopathy.

A 79 year old male acutely developed a Brown-Sequard syndrome two weeks following resection of renal cell carcinoma. The subsequent clinical course was marked by subacute progression of spinal cord signs. Pathologic studies showed extensive multifocal spinal cord necrosis that could not be attributed to vascular occlusion or to vasculitis. This case appears to be a rare example of paraneoplastic subacute necrotic myelopathy.

Aged↗

Pimozide-induced chronic hyperprolactinaemia and quantitative initiation of spermatogenesis in maturing rats.

When pimozide was given to maturing rats, a rise in the level of prolactin in the serum was accompanied by a fall in LH. There was also incomplete initiation of spermatogenesis as well as simultaneous adrenal hypertrophy. Bilateral adrenalectomy failed to prevent hyperprolactinaemia-induced antispermatogenic response, while a significant ameliorating effect was observed with LH, indicating that hyperprolactinaemia influenced the quantitative initiation of spermatogenesis by affecting the secretion of LH.

Adrenal Glands↗

Intracerebral arteriolar permeability to lanthanum.

Lanthanum, an electron-dense tracer, has been used extensively in the study of the structure of cell junctions. The present study was undertaken to determine whether the interendothelial junctions of normal intracerebral arterioles allow passage of lanthanum and to document the alterations occurring in these structures in acute hypertension. Perfusion of lanthanum for 12-40 minutes in control animals resulted in passage of tracer into arteriolar walls and into the extracellular compartment of the surrounding brain. The two principal mechanisms associated with tracer extravasation into the brain were diffuse passage through endothelial cytoplasm and through interendothelial spaces bypassing tight junctions. The latter finding has not been previously reported in normal cerebral arterioles and suggests that the tight junctions of these vessels are different from those of capillaries and consist of a meshwork of closely arranged maculae occludentes rather than complete circumferential occluding bands as was previously believed. Hypertensive animals showed accelerated passage of lanthanum, it being demonstrable not only in arteriolar walls but in capillary and venular walls and the surrounding neuropil after only 5 minutes of circulation. Passage of tracer through vessel walls occurred by the same routes as in control. In addition, increased numbers of pinocytotic vesicles were observed in the endothelium, confirming our previous studies that increased vesicular transport occurs in cerebral arteriolar endothelium in acute hypertension.

Animals↗