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Biomedical subjects

S Guha

Publications and source records attributed to S Guha.

At least 55 records · Page 3Linked to original sources

Co-ordination between membrane oriC sequestration factors and a chromosome partitioning protein, TolC (MukA).

oriC DNA in the hemimethylated (but not in the fully methylated) state reacts with an Escherichia coli K-12 outer membrane preparation. This reaction is drastically reduced when the membrane preparation of a seqA null mutant is used. An in vitro reconstitution of the activity was undertaken by adding a partially purified SeqA protein to a seqA mutant membrane without success. A possible reason for this failure might be a profound modification of the outer membrane of the seqA mutant (as revealed by the fact that membrane from the mutant sediments more slowly than that from the wild type during ultracentrifugation). There is also a reduction in the content of OmpF protein. Moreover, one of the minor outer membrane proteins involved in partitioning of newly synthesized chromosomes, the ToiC (MukA) protein, was also found to be downregulated in the seqA mutant. This is also true of the hobH mutant grown in a high-osmolarity medium. Mutants of both seqA and hobH stop dividing after hyperosmotic shock, forming filaments (as observed in dam mutants).

Bacterial Outer Membrane Proteins↗

Gastric emptying in early noninsulin-dependent diabetes mellitus.

UNLABELLED: The aims of this study were to determine in early noninsulin-dependent diabetes mellitus (NIDDM): (a) the prevalence of disordered gastric emptying of glucose; (b) the relationship between the blood glucose response to an oral glucose load and gastric emptying; and (c) the relationship between appetite and gastric emptying. METHODS: Sixteen patients (ages 39-79 yr) with recently diagnosed NIDDM consumed 350 ml water containing 75 g glucose and 99mTc-sulfur colloid while sitting in front of a gamma camera. Blood glucose concentrations were monitored immediately before and after the drink. Hunger and fullness were evaluated using visual analog scales. The results were compared to those obtained in 13 normal subjects of similar age and body mass index. All patients and control subjects were white and non-Hispanic. RESULTS: Gastric emptying was slightly slower in the NIDDM patients when compared to the control subjects (retention at 180 min 15.9 +/- 2.3% versus 3.8 +/- 1.0%, p < 0.001), but there was no significant difference in the 50% emptying time between the two groups. In the NIDDM patients, there was an inverse relationship between the magnitude of the increase in the blood glucose concentration and gastric emptying, e.g., between the area under the curve for blood glucose from 0-60 min and the intragastric retention of the drink at 60 min (r = -0.60, p < 0.05). In the NIDDM patients, fullness was greater (p < 0.005) both before and after the drink, and the score for hunger at 30 min was inversely related to the rate of gastric emptying (r = -0.52, p < 0.05). CONCLUSION: In patients with early NIDDM, gastric emptying of 75 g glucose is similar to that of normal subjects and is a significant determinant of the glycemic response.

Adult↗

A partially folded intermediate during tubulin unfolding: its detection and spectroscopic characterization.

The unfolding reaction of the dimeric protein tubulin, isolated from goat brain, was studied using fluorescence and circular dichroism techniques. The unfolding of the tubulin dimer was found to be a two-step process at pH 7. The first step leads to the formation of an intermediate conformation, stable at around 1-2 M urea, followed by a second step that was due to unfolding of the intermediate state. At pH 3, the urea-induced biphasic unfolding profiles obtained at pH 7 became a one-step process indicating that a stable intermediate was also formed at this pH. The intermediate at pH 3 was more stable toward urea denaturation than that at pH 7. The intermediate state has about 60% secondary structure, partially exposed aromatic residues, and less tertiary structure as compared to the native states. Also, hydrophobic surfaces were more exposed in the intermediate than in the native or unfolded states. These results indicate that the intermediate state observed during tubulin unfolding is not only distinct from both the native and unfolded forms but also possesses some properties characteristic of a molten globule.

Anilino Naphthalenesulfonates↗

The Saccharomyces SHP1 gene, which encodes a regulator of phosphoprotein phosphatase 1 with differential effects on glycogen metabolism, meiotic differentiation, and mitotic cell cycle progression.

The phosphoprotein phosphatase 1 (PP1) catalytic subunit encoded by the Saccharomyces GLC7 gene is involved in control of glycogen metabolism, meiosis, translation, chromosome segregation, cell polarity, and G2/M cell cycle progression. It is also lethal when overproduced. We have isolated strains which are resistant to Glc7p overproduction lethality as a result of mutations in the SHP1 (suppressor of high-copy PP1) gene, which was previously encountered in a genomic sequencing project as an open reading frame whose interruption totally blocked sporulation and slightly slowed cell proliferation. These phenotypes also characterized our shp1 mutations, as did deficient glycogen accumulation. Lysates from the shp1 mutants were deficient in PP1 catalytic activity but exhibited no obvious abnormalities in the steady-state level or subcellular localization pattern of a catalytically active Glc7p-hemagglutinin fusion polypeptide. The lower level of PP1 activity in shp1 cells permitted substitution of a galactose-induced GAL10-GLC7 fusion for GLC7; depletion of Glc7p from these cells by growth in glucose medium resulted in G2/M arrest as previously observed for a glc7cs allele but with depletion arrest occurring most frequently at a later stage of mitosis. The higher requirement of glycogen accumulation and sporulation for PP1 activity would permit their regulation via Glc7p activity, independent of its requirement for mitosis.

Base Sequence↗

Radioautography in cellular and molecular biology.

A general survey is presented on the most important applications of radioactive compounds as well on fresh as on fixed tissues, with and without immunological reactions, at light and electron microscopic levels. Its goal is to show their flexibility and their extended applications, in comparison with the non-radioactive methods. But radioautography applies as well to non-cellular aspects, such as electrophoretic and chromatographic techniques, permitting a complementary and even more detailed exploration of the molecules investigated at cellular levels. A rapid information is given on the exact denomination of the radioautographic methods, on hybridization in situ and in vitro, on the different blotting techniques used for DNA, RNA and proteins, on semi-quantitation and quantitation of DNA-RNA hybrids, on radioimmunodection by fluorography and on newer filmless radioautographic systems. The organ, body and pharmacological radioautographies belong to the nuclear medicine and have been evocated briefly.

Animals↗

The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest.

The retinoblastoma tumor suppressor protein (RB) binds several cellular proteins involved in cell cycle progression. Using the yeast two-hybrid system, we found that RB bound specifically to the protein BRG1. BRG1 shares extensive sequence similarity to Drosophila brahma, an activator of homeotic gene expression, and the yeast transcriptional activator SNF2/SW12. BRG1 contains an RB-binding motif found in viral oncoproteins and bound to the A/B pocket and the hypophosphorylated form of RB. BRG1 did not bind RB in viral oncoprotein-transformed cells. Coimmunoprecipitation experiments suggested BRG1 associates with the RB family in vivo. In the human carcinoma cell line SW13, BRG1 exhibited tumor suppressor activity by inducing formation of flat, growth-arrested cells. This activity depended on the ability of BRG1 to cooperate and complex with RB, as both an RB-nonbinding mutant of BRG1 and the sequestration of RB by adenovirus E1A protein abolished flat cell formation.

Amino Acid Sequence↗

Parental strand recognition of the DNA replication origin by the outer membrane in Escherichia coli.

The outer membrane of Escherichia coli binds the origin of DNA replication (oriC) only when it is hemimethylated. We report here the results of a footprinting analysis with the outer membrane which demonstrate that its interaction with oriC occurs mainly at the left moiety of the minimal oriC, where 10 out of 11 Dam methylation sites are concentrated. Two regions, flanking the Integration Host Factor (IHF) sites, are preferentially recognized at the minimum membrane concentration at which oriC plasmid replication is inhibited in vitro. We have identified the putative proteins involved in hemimethylated oriC binding and cloned one of the corresponding genes (hobH). The purified LacZ-HobH fusion protein specifically binds oriC DNA at the same preferential sites as the membrane. A mutant of the hobH gene reveals partial asynchronous initiation of DNA replication.

Amino Acid Sequence↗

Radiotherapy for parotid cancer.

BACKGROUND: Parotid malignancies represent a heterogeneous group of tumors primarily managed by surgical extirpation. Moderately high recurrence rates are seen after surgery alone, and postoperative radiotherapy has been used for patients with higher risks for local failure. METHODS: To assess the role of radiotherapy in the management of patients with malignant tumors of the parotid gland, the records of 68 patients receiving megavoltage therapy at our institution from 1966 to 1989 were reviewed. Patients were placed into three groups for analyses. Group I was composed of 41 patients receiving radiotherapy following total gross removal of parotid cancer by surgical procedures, varying from excisional biopsy through total parotidectomy. Radiation dose for this group ranged from 4,995 to 6,500 cGy. Group II was composed of 10 patients treated with radiotherapy after incisional biopsy or excision with positive margins. These patients received radiation doses of 4,000-9,470 cGy. Group III was composed of 17 patients receiving radiotherapy for a postsurgical local recurrence. Their radiation dose ranged from 4,300 to 8,400 cGy. RESULTS: Two of the 41 patients from group I developed a local recurrence. Two of these patients also developed distant metastases, one concurrent. Two of 10 group II patients failed locally, whereas three developed distant metastases. Only nine of the 17 patients in group III were controlled locally, and four patients developed distant dissemination. CONCLUSION: Total gross excision of parotid cancer, sparing facial nerve if possible and followed by regional radiotherapy, provides excellent rates of local control and survival with modest toxicity. Patients presenting postoperatively with gross residual tumor or recurrence after surgery should be considered for trials of more aggressive treatment with combined chemotherapy or altered fractionation schemes of irradiation.

Actuarial Analysis↗

The importance of social intervention in England's mortality decline: the evidence reviewed.

This paper examines the first phase of England's mortality decline, which commenced in the middle of the eighteenth century, and proceeded fitfully down to the end of the nineteenth. It finds that recent research in population history has weakened the explanation known as the McKeown thesis, but that the alternative synthesis, developed by Szreter, does not stand up well to a scrutiny of the evidence on infant mortality and morbidity. It concludes by pointing out that, contrary to the received version, diarrhoeal diseases continued in defiance of late-Victorian public health measures, but appear to have become less lethal, sharing in the general decline in the lethality of illness found by J. C. Riley for the second half of the nineteenth century.

History, Modern 1601-↗

The role of alpha-difluoromethyl ornithine as an adjuvant to immunotherapy in mice bearing transplantable tumors.

alpha-Difluoromethyl ornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), depletes cellular polyamine levels which is significantly correlated to neoplastic transformation. DFMO was used to modulate the growth rate of Ehrlich ascites carcinoma in mice and attempts were made to use DFMO as an adjuvant to immunotherapy. The therapeutic efficacy was estimated by measurement of polyamine levels of blood and ODC activity. Significant changes were also observed in the survival of the treated groups of animals, the implications of which have been discussed.

Adjuvants, Immunologic↗