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Biomedical subjects

S Davis

Publications and source records attributed to S Davis.

At least 343 records · Page 19Linked to original sources

Chemotherapy with cis-platin, doxorubicin, and cyclophosphamide (CAP) in patients with metastatic breast cancer.

Thirty-three evaluable patients with metastatic breast cancer (12 previously treated with adjuvant chemotherapy) were treated with a combination of cis-platin, doxorubicin, and cyclophosphamide (CAP). cis-Platin was given intravenously, 20 mg/m2, on days 1-3, doxorubicin, 40 mg/m2 i.v., on day 1, and cyclophosphamide, 200 mg/m2 i.v., on days 1-3. Cycles were repeated every 3 weeks. A complete response (CR) was obtained in 3 patients (9%) and a partial response (PR) in 18 (54%). The highest response rate was observed in soft tissue and in liver metastases. Median response duration was 48 weeks and median survival 93 weeks. Toxicity was moderate and consisted of alopecia (100%), gastrointestinal toxicity (86%), and myelosuppression (60%). We conclude that this regimen is active in the treatment of advanced breast carcinoma, with a generally acceptable tolerance, but further evaluations in Phase III studies are required.

Adult↗

Expression in recombinant vaccinia virus of the equine herpesvirus 1 gene encoding glycoprotein gp13 and protection of immunized animals.

The equine herpesvirus 1 (EHV-1) gene encoding glycoprotein 13 (gp13) was cloned into the hemagglutinin (HA) locus of vaccinia virus (Copenhagen strain). Expression of the gp13 gene was driven by the early/late vaccinia virus H6 promoter. Metabolically radiolabeled polypeptides of approximately 47 and 44 kilodaltons and 90 kilodaltons (glycosylated form) were precipitated with both polyclonal and gp13-specific monoclonal antibodies. Presentation of gp13 on the cytoplasmic membrane of cells infected with the recombinant gp13 vaccinia virus was demonstrated by immunofluorescence of unfixed cells. Inoculation of the recombinant gp13 vaccinia virus into guinea pigs induced neutralizing antibodies to both EHV-1 and vaccinia virus. Hamsters vaccinated with the recombinant gp13 vaccinia virus survived a lethal challenge with the hamster-adapted Kentucky strain of EHV-1. These results indicate that expression in vaccinia virus vectors of EHV-1 gp13, the glycoprotein homolog of herpes simplex virus gC-1 and gC-2, pseudorabies virus gIII, and the varicella-zoster virus gpV may provide useful vaccine candidates for equine herpesvirus infections.

Animals↗

Mandatory minute volume weaning in patients with pulmonary pathology.

This study evaluates mandatory minute volume (MMV) weaning in patients with pulmonary pathology. When weaning criteria were fulfilled, 22 patients were randomised to MMV and 18 to a control intermittent mandatory ventilation (IMV) group. With IMV weaning the ventilator rate was decreased by two breaths per minute at 3-4 hourly intervals during daylight hours. In the MMV group a target of 75% of the ventilator minute volume was set. All weans were considered complete four hours after the cessation of mechanical support, and were deemed successful if no further ventilation was required. The success rate was 86% in the IMV and 89% in the MMV group. MMV weaning was rapid (4.75 + 1.5 hrs) and proved less demanding on the ICU staff by providing a safe trial of spontaneous respiration, while retaining the facility for partial ventilation.

Adult↗

Dietary erucic acid therapy for X-linked adrenoleukodystrophy.

We investigated the biochemical and clinical efficacy of dietary erucic acid (C22:1) therapy for X-linked adrenoleukodystrophy (ALD). In a double-blind crossover study of patients who were on chronic oleic acid (C18:1) therapy, addition of erucic acid to the diet led to a further reduction in plasma hexacosanoic acid (C26:0) concentration. We treated 12 newly diagnosed ALD patients with a diet enriched with erucic acid and oleic acid for 2 to 19 months. Mean plasma C26:0 concentration decreased to normal by 4 weeks, and the C26:0 composition of plasma sphingomyelin and phosphatidylcholine became normal by 4 months on therapy. Fatty acid analysis of postmortem tissues from 1 boy treated for 10 months suggested that dietary erucic acid entered the heart, liver, adrenal gland, and brain. Eight patients remained on treatment long enough (mean, 12 +/- 3 months) to evaluate their clinical response; 6 of these patients with moderate to advanced disease deteriorated neurologically or showed progression of white matter disease on brain magnetic resonance imaging whereas 2 mildly affected patients remained clinically stable after 10 and 19 months. No adverse effects of the diet occurred. We conclude that dietary erucic acid therapy is effective in lowering plasma C26:0 to normal in ALD patients, and may prevent further demyelination in some mildly affected boys.

Adrenoleukodystrophy↗

Activated human blood monocytes trigger the antitumor activity of blood polymorphonuclear cells.

The purpose of these studies was to determine whether human peripheral blood polymorphonuclear cells (PMNC) can be directly activated by lymphokines or bacterial products to lyse tumorigenic cells under in vitro conditions. Preparations of PMNC with different levels of purity were isolated by countercurrent elutriation. PMNC were incubated with recombinant interferon gamma and muramyldipeptide, with lipopolysaccharide, or with the synthetic lipopeptide CGP 31362. Only PMNC preparations containing 3-5% mononuclear cells lysed allogeneic melanoma cells. Homogeneous populations of PMNC did not. The addition of 5% monocytes to homogeneous populations of PMNC triggered PMNC-mediated tumor lysis. Cell-to-cell contact was not required in this process since culture supernatant of blood monocytes incubated with lipopolysaccharide (but not with medium) could trigger tumor cell lysis by PMNC. PMNC lysed both allogeneic tumorigenic (melanoma) and allogeneic nontumorigenic (fibroblast) cells, whereas activated monocytes lysed only tumorigenic cells. In conclusion, PMNC are triggered to lyse target cells by blood monocytes activated by bacterial products or by lymphokines.

Adjuvants, Immunologic↗

5-Fluorouracil and isoprinosine in the treatment of advanced colorectal cancer. A limited phase I, II evaluation.

We studied the effects of 5-fluorouracil (5-FU) and isoprinosine (ISO) on 15 patients with previously untreated metastatic colorectal carcinoma. The patients were treated in a limited Phase I, II protocol. All patients received a fixed ISO dose of 4 g orally on days 1 through 5 of each cycle. Each cycle was repeated every 35 days. The first seven patients were treated with an initial 5-FU dose of 7.5 mg/kg intravenously (IV) on days 1 through 5, which was escalated to 11.5 mg/kg IV after the first course and to 13 mg/kg IV after the second course. The next eight patients were treated with an initial 5-FU dose of 11.5 mg/kg IV on days 1 through 5, which was escalated to 13 mg/kg IV on days 1 through 5. No major responses (complete or partial) were documented. Median survival for all evaluable patients was 33 weeks. Toxicity was predominantly gastrointestinal and hematologic and was considered moderate. Our data suggest that 5-FU and ISO, at the doses used, were ineffectual in the treatment of metastatic colorectal carcinoma.

Aged↗

Low-dose mitomycin and weekly low-dose doxorubicin combination chemotherapy for patients with metastatic breast carcinoma previously treated with cyclophosphamide, methotrexate, and 5-fluorouracil.

Forty-four evaluable patients with breast carcinoma previously treated with combination chemotherapy consisting of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) were treated with a combination chemotherapy regimen consisting of doxorubicin (A) (20 mg/m2 on days 1, 8, 15, and 22, repeated every 28 days) and mitomycin (MIT) (10 mg/m2 on day 1, repeated every 28 days). Five patients (11%) achieved a complete remission (CR) and 14 patients (32%) had a partial response (PR). The median duration of survival was 11.5 months and the median duration of response was 8 months for responders (CR and PR). Toxicity was moderate and consisted of neutropenia (74%), thrombocytopenia (25%), pneumonitis (11%), and cardiomyopathy (2%). The combination chemotherapy regimen A and MIT is an effective regimen for treating previously treated with CMF.

Antineoplastic Combined Chemotherapy Protocols↗

Incidence of cancer of the esophagus in the US by histologic type.

Data from nine US population-based cancer registries participating in the Surveillance, Epidemiology, and End Results (SEER) program from 1973 through 1982 were analyzed to examine demographic characteristics related to the occurrence of the two major types of cancer of the esophagus. The overall annual incidence rate per 100,000 persons was 2.6 for squamous cell carcinoma and 0.4 for adenocarcinoma. The sex ratio for adenocarcinoma varied from one age group to the next and was highest in the 50- to 59-year-old group. It was relatively the same for squamous cell carcinoma. The male-to-female ratio was higher for adenocarcinoma (seven in whites and 10 in blacks) than for squamous cell carcinoma (three and four, respectively). The highest sex-specific ratio for adenocarcinoma occurred in the lower third of the esophagus. Blacks had a fourfold to fivefold higher rate of squamous cell carcinoma than whites, but the rate of adenocarcinoma in blacks was 30% of the rate in whites. The incidence of squamous cell carcinoma in black men and women increased by approximately 30% between 1973 and 1982, and the rate of adenocarcinoma among white men increased 74%. Nearly half of the squamous cell carcinomas occurred in the middle of the esophagus, whereas the majority (79%) of the adenocarcinomas arose in the lower third. These data suggest that the two major histologic types of esophageal cancer may be of different etiologic origin.

Adenocarcinoma↗

Hepatic clearance and metabolism in the rat of a human breast cancer associated glycoprotein (GCDFP-15).

Gross Cystic Disease Fluid Protein (GCDFP-15) is a 60,000 dalton glycoprotein isolated from human breast cyst fluid, composed of four 15,000 dalton monomers. Carbohydrate analysis indicates that each monomer has a single carbohydrate chain of the complex type. GCDFP-15 intravenously injected into rats showed a rapid circulatory clearance, the rate of clearance being faster in female animals [t1/2 = 12.8 (+/- 2.0) min. females, and 16.7 (+/- 2.6) min. males]. The major organs of clearance were the liver (70%) and kidneys (15%). Immunoperoxidase staining showed localization in Kupffer cells and the proximal convoluted tubules of the kidney. Removal of sialic acid from GCDFP-15 resulted in a more rapid clearance (t1/2 = 2.2 min) by the liver (85%). This clearance was inhibited by coinjection of asialo alpha 1 acid glycoprotein. About 3% of GCDFP-15 was excreted in bile with a transit time through the liver of 38 min. Examination of the uptake of GCDFP-15 by isolated rat Kupffer cells showed that yeast mannan, fucosylated BSA, and carcinoembryonic antigen (CEA) failed to inhibit uptake, though the binding of GCDFP-15 was clearly saturable. This suggests that a novel receptor system on the rat Kupffer cell may be responsible for GCDFP-15 clearance.

Animals↗

Points and endpoints: a size/spacing constraint for dot grouping.

One-dimensional arrangements of dots immediately group into contours. It is reported that, when these contours participate in certain larger arrangements, there is an abrupt point at which the percept changes as a function of dot spacing (or density along the contour). Closely spaced arrangements give rise to subjective effects involving apparent brightness and depth, whereas sparsely spaced ones do not. The effects are most clear in configurations that involve endpoints and possible occlusions. For these configurations, densely dotted contours are perceptually equivalent to solid ones, but sparse ones are not. This change in percept occurs abruptly and consistently at a dot to space ratio of 1:5, when the dot density is normalized by dot size, and this point is called the size/spacing constraint. It holds only for dots of the order of 1 min visual angle in diameter when small to modest contrast values are used. The subjective effects are not present for dotted contours (or even for solid ones) that are smaller (less than 0.5 min), and differ for contours that are larger (greater than 10 min). To demonstrate the significance of size/spacing constraints for early vision, a framework for grouping consisting of processes at many different levels is outlined, and the requirements for the earliest one (orientation selection) are sketched in greater detail. The size/spacing constraint follows directly from one of these requirements--receptive field structure--and seems to indicate a switch from early orientation-selection processes to later ones.

Attention↗

Increased mRNA expression of a laminin-binding protein in human colon carcinoma: complete sequence of a full-length cDNA encoding the protein.

Reliable markers to distinguish human colon carcinoma from normal colonic epithelium are needed particularly for poorly differentiated tumors where no useful marker is currently available. To search for markers we constructed cDNA libraries from human colon carcinoma cell lines and screened for clones that hybridize to a greater degree with mRNAs of colon carcinomas than with their normal counterparts. Here we report one such cDNA clone that hybridizes with a 1.2-kilobase (kb) mRNA, the level of which is approximately equal to 9-fold greater in colon carcinoma than in adjacent normal colonic epithelium. Blot hybridization of total RNA from a variety of human colon carcinoma cell lines shows that the level of this 1.2-kb mRNA in poorly differentiated colon carcinomas is as high as or higher than that in well-differentiated carcinomas. Molecular cloning and complete sequencing of cDNA corresponding to the full-length open reading frame of this 1.2-kb mRNA unexpectedly show it to contain all the partial cDNA sequence encoding 135 amino acid residues previously reported for a human laminin receptor. The deduced amino acid sequence suggests that this putative laminin-binding protein from human colon carcinomas consists of 295 amino acid residues with interesting features. Containing only two cysteine residues, the protein does not have consensus sequences for asparagine-linked glycosylation, amphipathic alpha-helix, or the N-terminal leader signal sequences for entry into endoplasmic reticulum, although hydrophobic segments for potential membrane associations exist. There is an unusual C-terminal 70-amino acid segment, which is trypsin-resistant (no lysine or arginine) and highly negatively charged (13 aspartic plus glutamic residues). Within this segment are five repeats of (Asp/Glu)-Trp-(Ser/Thr); two of these are nearly tandem repeats of Thr-Glu-Asp-Trp-Ser-Ala-Xaa-Pro.

Amino Acid Sequence↗

Epidemiological characteristics of adenocarcinoma of the gastric cardia and distal stomach in the United States, 1973-1982.

Data from the Surveillance, Epidemiology, and End Results (SEER) programme of the National Cancer Institute were utilized to estimate the incidence of adenocarcinoma of the gastric cardia and distal stomach in the US in order to determine whether the epidemiological features of these diseases differ. Based upon 12,562 histologically confirmed cases identified, the annual incidence of gastric cardia adenocarcinoma was 1.1 per 100,000 people and for the distal stomach 3.8 per 100,000. The male-to-female ratio for adenocarcinoma arising in the cardia was 7.0, versus 2.2 for that arising in the distal stomach. The sex ratio shifted across age groups for the gastric cardia and was highest for the 50-59 year age group, but remained relatively stable across age groups for cancers of the distal stomach. Over the decade studied, the sex ratio decreased from 8.0 to 4.6 for gastric cardia tumours, but remained constant for adenocarcinoma of the distal stomach. Blacks were 2.5 times more likely to develop adenocarcinoma of the distal stomach than whites, but had a 50% lower risk of gastric cardia tumours than whites. These results support an emerging concept that adenocarcinoma of the gastric cardia, gastro-oesophageal junction and distal oesophagus may comprise a group of disease which is aetiologically distinct from distal gastric tumours.

Adenocarcinoma↗

Two one-step methods for household screening and interviewing using random digit dialing.

Random digit dialing is commonly used to select controls for epidemiologic studies. The traditional method of random digit dialing entails screening households to obtain a pool of eligible subjects and then selecting a random sample to serve as controls. Two random digit dialing methods are described in which household screening and interviewing are combined into one step. The advantages and limitations associated with both of the one-step methods and the traditional two-step approach are discussed.

Data Collection↗

Acute nonlymphocytic leukemia and residential exposure to power frequency magnetic fields.

Recent research has suggested that nonionizing radiation in the form of power-frequency magnetic fields may play some role in carcinogenesis in general and in acute nonlymphocytic leukemia in particular. Much of the epidemiologic evidence is preliminary in nature and the methods of previous studies have been criticized. In order to further evaluate this hypothesis, a population-based case-control study of adult acute nonlymphocytic leukemia and residential exposure to power-frequency magnetic fields was carried out in western Washington state. Analyses were based on 114 cases who were newly diagnosed from 1981 to 1984 and identified from a population-based cancer registry, and 133 controls who were chosen from the study area by random digit dialing. Magnetic field exposure was estimated from external electrical wiring configurations within 140 ft (42.7 m) of each subject's residence. In addition, magnetic fields were measured inside the subject's residence at the time of interview. Neither the directly measured magnetic fields nor the surrogate values based on the wiring configurations were associated with acute nonlymphocytic leukemia.

Acute Disease↗