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S Grimes

Publications and source records attributed to S Grimes.

15 recordsLinked to original sources

Gastrimmune raises antibodies that neutralize amidated and glycine-extended gastrin-17 and inhibit the growth of colon cancer.

The effect of gastrin neutralization was evaluated on the in vivo growth of the rat colon line, DHDK12, which expressed cholecystokinin B/gastrin receptors and secreted glycine-extended gastrin-17 (G17). Gastrin neutralization was achieved by administration of the immunogen, Gastrimmune, which is composed of the amino terminal portion of G17 linked to a diphtheria toxoid. A rat-specific version of Gastrimmune was used to preimmunize rats, with control animals receiving diphtheria toxoid only. The antibodies raised neutralized both carboxy-amidated and glycine-extended G17. The tumor was implanted into the muscle layer of the abdominal wall, and rats immunized with Gastrimmune had significantly reduced median cross-sectional tumor areas (70.2% reduction; P = 0.005) and weights (56.5% reduction; P = 0.0078)) when compared to control rats. Histological analysis revealed that the tumors had an enhanced degree of necrosis, with the area of viable tumor in the Gastrimmune-immunized rat reduced to 40.3% compared to 58.6% in the control rats (P = 0.003). Immunization with Gastrimmune raised antibodies that inhibited the growth of a rat colon tumor. This could have been mediated by neutralization of both serum G17 and cell-associated precursor gastrin molecules.

Amino Acid Sequence

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Family Planning Services

Anti-gastrin antibodies raised by gastrimmune inhibit growth of the human colorectal tumour AP5.

The neutralising ability of rabbit anti-gastrin-17 (G17) antiserum raised by Gastrimmune, an immunogen constructed of the N-terminal portion of human G17 conjugated to diptheria toxoid (DT), was evaluated. The anti-serum (denoted anti-G17: DT) was shown to displace 125[I] G17 from the gastrin receptors on AR42J cells. The therapeutic effect of the rabbit anti-G17:DT anti-serum was evaluated on a freshly derived human colorectal cancer cell line, AP5, which was shown to express both gastrin receptors and gastrin immunoreactivity as assessed by immunocytochemistry. Rabbit anti-G17:DT anti-serum was shown to block basal in vitro growth of AP5 cells when used at an antigen binding capacity of 3.75 x 10(-9) M. The same dilution of anti-serum completely reversed growth stimulated by human G17 at concentrations of 1 x 10(-10) and 1 x 10(-9) M but did not inhibit growth at 1 x 10(-8) M G17. When AP5 was grown as a xenograft in nude mice, the sensitivity to the proliferative effect of human G17 was maintained. In addition, the basal growth of AP5 xenografts was significantly reduced by i.v. infusion of rabbit anti-G17:DT anti-serum when compared to treatment with rabbit anti:DT control anti-serum. Thus anti-G17:DT antibodies raised by Gastrimmune may be of clinical value in gastrin-sensitive tumours.

3T3 Cells

Sumatriptan and cerebral perfusion in healthy volunteers.

1. The effect of sumatriptan on regional cerebral perfusion was studied in healthy volunteers. 2. Intravenous sumatriptan (2 mg) had no detectable effect on regional cerebral perfusion as measured using a SPECT system with 99technetiumm labelled hexemethylpropyleneamineoxime. 3. Sumatriptan had no effect on pulse, blood pressure or ECG indices. 4. All six volunteers experienced minor adverse effects during the intravenous infusion.

Adult

RNA dependence of the bacteriophage phi 29 DNA packaging ATPase.

The activity of the DNA packaging adenosine triphosphatase (ATPase) of the Bacillus subtilis bacteriophage phi 29 is dependent upon prohead RNA. The 174 nucleotide viral-encoded RNA is positioned on the head-tail connector at the portal vertex of the phi 29 precursor shell (prohead). Here, the RNA interacts with the ATP-binding gene 16 product (gp16) to constitute the DNA-packaging ATPase and initiate DNA packaging in vitro. Both the prohead connector (gene 10 product, gp10) and gp16 may utilize an RNA recognition motif characteristic of a number of RNA-associated proteins, and the binding of gp16 by proheads shields the prohead RNA from RNase A. The ATPase activity of gp16 is stimulated fourfold by RNA and tenfold by proheads with RNA. RNA is needed continuously for the gp16/RNA ATPase activity and is essential for the gp16/prohead ATPase activity. The prohead, with its connector, RNA and associated gp16 in an assembly-regulated configuration, hydrolyzes ATP and drives phi 29 DNA translocation.

Adenosine Triphosphatases

Impact of crime on the rural elderly.

Two hundred and seven persons over 65 years of age were interviewed to determine the impact of crime on their lives. The setting was during a much publicized series of assaults on the rural elderly in their homes. Seventy two per cent were upset, 40% of the total were moderately upset and 26% suffered a major upset. Females and those over 75 years old were most upset. Some aspect of change of lifestyle was found in the vast majority.

Age Factors

In vitro packaging of bacteriophage phi 29 DNA restriction fragments and the role of the terminal protein gp3.

Restriction fragments of bacteriophage phi 29 DNA-gp3 (DNA-gene product 3 complex) were packaged in a completely defined in vitro system that included purified proheads, the DNA packaging protein gp16 and ATP. Both left and right end DNA-gp3 fragments were packaged in this system, in contrast to the oriented and selective packaging of left end DNA-gp3 fragments in extracts; left ends could be packaged quantitatively in the defined system, while the packaging efficiency of right ends was generally about threefold lower. In addition, certain internal (non-end) DNA fragments were packaged at efficiencies of about 10% to 15%. Digestion of the gp3 with trypsin or proteinase K reduced the packaging of whole-length DNA by a factor of 2 or 4, respectively, and removal of the gp3 from whole-length DNA or end fragments with piperidine reduced packaging to the level of internal fragments. Though the terminal protein gp3 was non-essential for DNA translocation in the defined system, it stimulated packaging of left and right end fragments, and stabilized packaging of the left end. The packaging of end and internal DNA fragments of the related phage M2Y into phi 29 proheads was similar to that of phi 29 DNA fragments, and certain fragments of lambda DNA were packaged at the efficiency of the internal phi 29 DNA fragments. Selective packaging of DNA-gp3 left ends was restored by the addition of bacterial cell extracts or glycerol to the defined system, and these packaging conditions discriminated between phi 29 and M2Y DNAs that have distinct terminal proteins.

Bacillus subtilis

Cleaving the prohead RNA of bacteriophage phi 29 alters the in vitro packaging of restriction fragments of DNA-gp3.

In vitro packaging of restriction fragments of the bacteriophage phi 29 DNA-gp3 (DNA-gene product 3 complex) in the defined system was dependent on prohead RNA. Truncated prohead RNAs were obtained by in situ RNase A digestion, isolated and sequenced. Proheads having the intact 174 base RNA were compared to proheads having RNAs of 120, 95, 71, 69 or 54 bases for the capacity to package the DNA-gp3 left and right ends and internal (non-end) fragments generated by the restriction enzymes EcoRI, HpaI and BstNI. Proheads with the 174 or 120 base RNAs packaged both left and right ends; internal fragments were packaged more efficiently by proheads with the 120 base RNA. Proheads with the 95 base RNA packaged DNA-gp3 left ends and internal fragments efficiently, but lost the capacity to package right ends. Only internal fragments were packaged by proheads with the 71 base RNA, and proheads having 69 or 54 base RNAs were inactive. RNA-free proheads were effectively reconstituted with purified 174 and 120 base RNAs to produce particles similar in biological activity to the proheads from which the RNAs were isolated. The 95 base RNA was the smallest RNA of the group that could reconstitute the prohead and direct fragment packaging, although packaging was inefficient. Alteration of the specificity of DNA fragment packaging with truncated prohead RNAs has delineated RNA domains that function in DNA-gp3 recognition and prohead binding.

Bacteriophage lambda

A rat histone H4 gene closely associated with the testis-specific H1t gene.

A rat histone H4 gene closely associated with the testis-specific H1t gene was isolated by screening the Sargent-Bonner rat genomic library using cloned human histone genes as probes. Both the H4 gene and the H1t gene are located on a 7-kb EcoRI genomic DNA fragment. Although the deduced amino acid sequence of the rat H4 histone is identical to that of the sequence of human histone H4, the nucleotide sequence of the coding region differs significantly from the coding region of the human H4 gene. Moreover, the relative spacing between the 5'-consensus sequence elements is unique for an H4 gene. S1-nuclease protection analyses reveal that both the H4 and H1t mRNA species are present in a fraction of rat testis cells highly enriched in pachytene spermatocytes, while only the H4 mRNA species is present in a rat myeloma cell line (Y3-Ag1.2.3). During a 1-h hydroxyurea treatment of the Y3 cells, which produces a 99% inhibition of DNA synthesis, the level of this H4 mRNA drops by only 50%, indicating that the stability of this mRNA is only partially coupled with DNA synthesis.

Amino Acid Sequence

Induction of latent immunological memory in genetically nonresponsive mice.

C57BL/10 mice exhibit major histocompatibility complex linked nonresponsiveness to hen egg white lysozyme (HEL). When these animals are primed with HEL in Freund's complete adjuvant (FCA), their secondary splenic plaque forming cell responses to aqueous HEL challenge are minimal to nonexistent. This notwithstanding, we show here that concomitant priming with both HEL and keyhole limpet hemocyanin (KLH) leads to an enhanced response to the HEL component following secondary challenge with an HEL-KLH conjugate. This enhancing effect can be transferred by nylon wool nonadherent spleen cells from HEL/FCA primed animals. Adoptive transfer studies with fractionated spleen cell populations suggest also that B cells are primed in these animals. Thus, animals which are incapable of mounting a secondary response to this antigen nevertheless appear to be primed at both the T-cell and B-cell levels following exposure to the antigen in FCA. The implications of this finding are discussed.

Animals

A defined system for in vitro packaging of DNA-gp3 of the Bacillus subtilis bacteriophage phi 29.

The bacteriophage phi 29 DNA-gene product 3 complex (DNA-gp3) has been efficiently packaged into proheads in a completely defined in vitro system. The phi 29 DNA packaging protein gp16, the product of gene 16, was overproduced in Escherichia coli and purified to near homogeneity. The purified gp16 packaged 23% of the DNA-gp3 added to purified proheads in the defined mixture, while gp16 in an extract of phage-infected cells packaged 26% of the DNA-gp3. No host proteins were required in the defined system. ATP-dependent packaging of DNA-gp3 in the defined system was optimal with approximately equal to 100 copies of gp16 per DNA-gp3, an amount similar to the production of gp16 per DNA-gp3 in phi 29-infected cells.

Adenosine Triphosphate

Cellular basis of genetic nonresponsiveness to egg white lysozyme.

Utilizing radiation chimeras, we have investigated the cellular level at which the low immunological responsiveness to egg white lysozyme C57Bl/10 mice is expressed. Both NR----F1 (responder) and F1----NR combinations were assessed. The results demonstrate that C57Bl/10 bone marrow can give rise to hen egg white lysozyme responsive cells, but this response requires that the antigen be presented by cells derived from high responder animals.

Animals

ApoA-I/ApoA-II ratios in plasmas of vegetarians.

Diets low in fat and cholesterol and high in P/S ratio are accompanied by low HDL-cholesterol levels. Short-term experimental feeding of such diets demonstrates that the HDL2 fraction is reduced preferentially. In order to ascertain whether the HDL2 lowering effects persist over the long-term, apolipoprotein A-I/A-II ratios, which are indices of the HDL2 relative to HDL3 in plasma, were measured in three groups of vegetarians (n = 35) who had been eating vegetarian diets for 1 to more than 5 years varying in cholesterol contents from less than 10 to 300 mg/d, fat between 30% to 50% of calories, and P/S ratio between 0.7-2.5. Concentrations of apoA-I were lower in those eating the least cholesterol and the highest P/S ratio, ie, apoA-I correlated positively with dietary cholesterol (r = 0.38, P less than 0.05), and both apoA-I and the A-I and the A-I/A-II ratio correlated negatively with the ratio of polyunsaturated-to-saturated (P/S) fatty acids (r = -0.39, P less than 0.05, and r = -0.41, P less than 0.02, respectively). There was no significant correlation between apoA-I, apoA-II, the A-I/A-II ratio or the high-density lipoprotein cholesterol/apoA-I ratio and consumption of total calories, fat, protein, or carbohydrate. Since the A-I/A-II ratio is much higher in HDL2 than in HDL3, these data suggest that cholesterol intake and the P/S ratio are important long-term dietary determinants of plasma HDL2 levels. Thus, in vegetarians, despite a reduced risk of coronary heart disease, the high-density lipoprotein cholesterol (HDL-C) and especially HDL2 concentrations were low. More work is needed to elucidate this interesting paradox.

Adult

Apolipoprotein E levels in vegetarians.

Vegetarians are known to have low lipoprotein lipid and apolipoprotein Al and B levels. Since dietary cholesterol has recently been shown to have important effects on apolipoprotein E (apo E) metabolism, we measured plasma apo E levels in three groups of vegetarians. Group I (n = 36) consumed less than 10 mg cholesterol daily and 42% of calories as fat (P:S ratio 2.6). Group II (n = 10) and Group III (n = 18) consumed 97 and 179 mg cholesterol daily, and 35% of calories as fat (P:S ratios 0.7 and 0.9) respectively. Compared to control values, vegetarian plasma cholesterol and triglyceride levels were decreased by 10%-30% and 30%-55%. Plasma apo E levels were decreased equally in all groups by 35% (2.4 +/- 0.1 mg/dl versus 3.6 +/0 0.1 mg/kl, P less than .001). Plasma apo E levels were increased in parallel with lipid levels in pregnant vegetarians but were not different from non-lactating vegetarians in postpartum lactating women. Decreased apo E levels did not correlate with relative body weight, P:S ratio or intake of fat, carbohydrates or protein. Since all vegetarian diets studied were low cholesterol diets, decreased cholesterol intake may contribute to the low apo E levels. The apparent modification of apo E metabolism by vegetarian diets may be important in mediating effects of lipid lowering diets on atherogenesis.

Apolipoproteins