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Biomedical subjects

C Smith

Publications and source records attributed to C Smith.

At least 757 records · Page 42Linked to original sources
PubMed1989

Structure of cDNA clones coding for human type II procollagen. The alpha 1(II) chain is more similar to the alpha 1(I) chain than two other alpha chains of fibrillar collagens.

Overlapping cDNA clones were isolated for human type II procollagen. Nucleotide sequencing of the clones provided over 2.5 kb of new coding sequences for the human pro alpha 1(II) gene and the first complete amino acid sequence of type II procollagen from any species. Comparison with published data for cDNA clones covering the entire lengths of the human type I and type III procollagens made it possible to compare in detail the coding sequences and primary structures of the three most abundant human fibrillar collagens. The results indicated that the marked preference in the third base codons for glycine, proline and alanine previously seen in other fibrillar collagens was maintained in type II procollagen. The domains of the pro alpha 1(II) chain are about the same size as the same domains of the pro alpha chains of type I and type III procollagens. However, the major triple-helical domain is 15 amino acid residues less than the triple-helical domain of type III procollagen. Comparison of hydropathy profiles indicated that the alpha chain domain of type II procollagen is more similar to the alpha chain domain of the pro alpha 1(I) chain than to the pro alpha 2(I) chain or the pro alpha 1(III) chain. The results therefore suggest that selective pressure in the evolution of the pro alpha 1(II) and pro alpha 1(I) genes is more similar than the selective pressure in the evolution of the pro alpha 2(I) and pro alpha 1(III) genes.

Amino Acid Sequence↗
PubMed1989

Effects of interleukin-1 on hematopoietic progenitors: evidence of stimulatory and inhibitory activities in a primate model.

The effects of recombinant human interleukin-1 rhIL-1 beta (rhIL-1b) on hematopoietic recovery following chemotherapy in a primate model were investigated. Cynomolgus monkeys received 1 microgram/kg/day rhIL-1b intravenously for 2, 7, and 14 days following 5-Fluorouracil (5-FU) treatment (75 mg/kg x 2 days). Compared with controls, a significantly shortened time to achieve an absolute neutrophil (ANC) count over 500/microL was observed in animals receiving 2- and 7-day courses of rhIL-1b (17 v 30 days), while animals receiving a 14-day course of rhIL-1b achieved an ANC over 500/microL by 23 days. Concomitantly, a marked increase in granulocyte-macrophage colonies (CFU-GM) was observed at 14 days following 5-FU in animals receiving 2- and 7-day rhIL-1b courses. In animals receiving a 14-day rhIL-1b course, a significant increase in CFU-GM relative to control was not seen until 21 days post 5-FU. Utilizing a serum-free colony assay system, a 50% inhibition of normal marrow CFU-GM growth was observed with the addition of sera obtained on day 9 post 5-FU from animals receiving rhIL-1b for 14 days. Sera obtained at any time from animals receiving 2- and 7-day rhIL-1b treatment did not show any growth inhibition. Addition of antibodies to TNFa to the coculture assay abrogated the CFU-GM growth inhibition. TNFa levels in sera with the inhibitory activity was relatively high (918 pg/mL). Our data indicate that rhIL-1b enhances hematopoietic recovery following 5-FU if administered for short periods of time (less than 7 days), whereas prolonged administration has a counterproductive effect that is due in part to the induction of TNFa production.

Animals↗
PubMed1989

Circadian variations of human lymphocytes are not responsible for contradictory or variable results in studies of IL-2 production.

Efforts to correlate various immunological disorders with alterations in IL-2 production in vitro have led to highly variable and often contradictory results. One possible contributing factor to these results could be the existence of circadian variations in the capacity of lymphocytes to produce IL-2 in culture. Although there were reasons to suspect that such variations might exist, the present study revealed no significant variations in 6 of 10 normal subjects in three experiments or in the mean values for all subjects at each of three sample acquisition times. In addition, no subject exhibited circadian variations in all three experiments. Since it was possible that failure to detect variations was due to selection of an inappropriate mitogen or inappropriate culture conditions, 2 mitogens and various culture conditions were used. Circadian variation was noted for only one subject out of eight under only one set of conditions. This suggests that circadian variations are not responsible for variable or contradictory results which have been reported. Therefore, the recently reported circadian variations in T helper to T suppressor ratios do not seem to significantly affect mitogen-induced IL-2 production.

Adult↗
PubMed1989

Effects of IL-1 on hematopoietic progenitors after myelosuppressive chemoradiotherapy.

Recently it has been recognized that IL-1 plays an important role in hematopoietic regulation. Administration of 5-fluorouracil (5-FU) to mice causes prolonged neutropenia. rHIL-1 injected to mice after 5-FU, accelerated the recovery of hematopoietic progenitors and blood neutrophils. The combination of rhIL-1 and rhG-CSF reduced the neutropenic period significantly. Sublethal irradiation of mice induced profound neutropenia for 3 weeks which was associated with 80% mortality. Administration of rhIL-1 20 hours prior to or 2 hours post irradiation resulted in a significantly improved survival and rapid recovery of the neutrophil count. IL-1 administered alone or in combination with other colony stimulating factors to spontaneous breast tumor bearing mice following 5-FU therapy resulted in a rapid recovery of neutrophils, improved survival, and markedly reduced the tumor mass. Experiments in primates demonstrated that rhIL-1 administered to 5-FU treated animals shortened the neutropenic period from 30 to 17 days and increased the number of marrow progenitors responsive to other CSFs. Prolonged administration of IL-1 (14 days) to these animals resulted in a delayed neutrophil recovery as compared to animals receiving short courses of IL-1. rhIL-1 administered to primates receiving marrow grafts after lethal irradiation, did not result in rapid hematopoietic recovery. In humans, studies with CD-34 positive marrow cells showed that IL-1 had a radioprotective effect on a committed and early marrow progenitors. These data show the therapeutic potential of IL-1 in the treatment of chemoradiotherapy induced myelosuppression.

Animals↗
PubMed1989

Colorectal cancer in patients younger than 40 years of age.

To assess prognostic factors in patients who develop colorectal cancer before the age of 40 years, a 30-year experience from 1956 through 1985 was reviewed. There were 50 patients ranging in age from 7 to 39 years. Five cases were associated with either ulcerative colitis (2) or familial polyposis (3). The most common presenting symptoms were abdominal pain (66 percent), hematochezia (60 percent), change in bowel habit (41 percent) and weight loss (30 percent). On pathologic staging (N = 44), only 14 of 44 (31 percent) had a Dukes' stage A or B lesion, 20 (45 percent) had Dukes' stage C, and the remaining 10 (23 percent) had distant metastases at the time of surgery. Five-year survival rate was 28 percent with a disease-free survival rate of 18 percent. Median survival was only 28 months. Negative prognostic factors were Dukes' stage C/D (P less than .001), symptom duration of longer than 3 months (P = .01), noncaucasian ancestry (P = .01), and poorly differentiated histology (P = .06). In contrast to older patients with colorectal cancer, only 1 of 30 (3 percent) patients with stage C D disease was disease-free at 5 years. In view of the poor survival rate associated with both delay in diagnosis and the presence of advanced disease, it was concluded that young patients presenting with the symptoms listed above need early, aggressive evaluation for possible colorectal cancer.

Adenocarcinoma↗
PubMed1989

Fine-needle aspiration biopsy in the diagnosis of recurrent and metastatic intraabdominal malignancies.

To evaluate the efficacy of directed percutaneous fine-needle aspiration (FNA) biopsy in the diagnosis of recurrent and metastatic intraabdominal malignancies, we reviewed our experience from 1981 to 1988. Seventy-three aspirations were performed in 73 patients. Forty-six patients with a previously treated malignancy had aspiration to diagnose either locally recurrent or metastatic disease. The remaining 27 patients had liver aspiration to rule out metastases from suspected or unknown primary sites. Computed tomography and ultrasonography were equally effective in providing diagnostic material, which was obtained from 68 of 73 aspirates. No serious morbidity occurred. Fifty-seven patients had a metastatic or recurrent malignancy, and 3 had primary hepatocellular carcinoma. Fine-needle aspiration biopsy correctly identified 51 (85 percent) of these 60 cases. There were no false-positive results and five false-negative results. Aspiration results obviated the need for a diagnostic laparotomy in 49 of the 60 patients with malignancy (82 percent). We conclude that directed percutaneous FNA biopsy is a safe and accurate method of diagnosing recurrent and metastatic intraabdominal malignancies.

Abdominal Neoplasms↗
PubMed1989

Hemolysis during long-term extracorporeal membrane oxygenation.

We studied the cause of hemolysis during extracorporeal membrane oxygenation (ECMO) by monitoring hematologic and coagulation profiles in seven consecutive infants treated with this procedure. A constrained vortex pump was used in all patients, and the average duration of ECMO was 224 +/- 111 (SD) hours. In all patients, plasma free hemoglobin was low during the first 48 hours after the initiation of ECMO. Later, when visible clots appeared in the ECMO circuit, plasma hemoglobin progressively rose. A rise in the level of fibrin degradation products and a fall in the fibrinogen level were observed concurrently with a rise in the plasma hemoglobin level. After complete circuit changes in six patients, plasma free hemoglobin, fibrin split products, and fibrinogen all returned to baseline values. Neither circuit component changes nor exchange transfusion was effective in normalizing the levels of plasma free hemoglobin, fibrin split products, and fibrinogen. We conclude that when ECMO is administered for prolonged periods, circuit thrombosis occurs and hemolysis ensues. Additional studies are needed to assess the contribution of the constrained vortex pump to this process.

Exchange Transfusion, Whole Blood↗
PubMed1989

Avoidance performance in rat enhanced by postlearning paradoxical sleep deprivation.

This series of experiments investigates possible relations between increases in paradoxical sleep (PS), persisting for several days after an avoidance training, and improvement of retention performance that occurred 3 days following partial training in a brightness discrimination Y-maze shock-avoidance task. Sprague-Dawley rats were trained in the Y-maze and PS deprived for 24 h either immediately or 24, 48, or 72 h following initial training. Contrary to what was expected, the results indicated that PSD immediately following the training session enhanced the avoidance performance after a 7-day retention interval. PSD at later times had no effect. Experiment 2 indicated that this effect was obtained only for PS-deprived animals and not for those placed in the PSD situation, but on larger platforms. Thus enhancement of the avoidance performance was not due to increases in stress or arousal caused by PSD-associated factors. Experiment 3 showed that the facilitative effect of a non-delayed 24-h PSD was obtained immediately thereafter as well as 24 h later, demonstrating that this effect was not due to any PS rebound which might have occurred following the PSD. Alternative explanations for these unexpected results are discussed.

Animals↗
PubMed1989

Contraceptive use patterns in Matlab, Bangladesh: insights from a 1984 survey.

An experimental maternal and child health and family planning programme has been in existence in Matlab for almost 10 years. During this time the project has achieved remarkable success in the area of family planning. Based upon a 1984 survey, this study examines the pattern of contraceptive use in the Matlab treatment area, and contrasts it with the regular government programme in the neighbouring comparison area. Important differences between the two areas are observed, with the treatment area characterized by substantially higher levels of current contraceptive use, greater reliance upon temporary methods for birth spacing and, among acceptors of sterilization, more prior experimentation with other methods. In the comparison area lower rates of contraceptive use are observed, with heavy reliance upon tubectomy for limiting family size. The findings suggest that an intensive and innovative family planning programme in rural Bangladesh can achieve success not only in terms of contraceptive prevalence, but can also attract users interested in child spacing and others wanting to limit their family size, by offering the widest range of contraceptive methods.

Adult↗
PubMed1989

Is there atypical handedness in schizophrenia?

Ninety-three schizophrenic patients and 105 normal controls were tested in a single session on an 8-item repeat-administration handedness test. The schizophrenic group, in contrast to the normal controls, showed a shift in the distribution away from right-handedness, which was due to an increase in the proportion of mixed-handers. Additional analyses revealed that the increase in mixed-handedness was largely due to an increase of within-item variability in the schizophrenic group, which we refer to as ambiguous handedness. Nearly 20% of the schizophrenic patients were inconsistent on 3 or more items compared with 3.8% of the normal controls. This increased incidence of atypical handedness is discussed within the context of disorders of attention and neurodevelopment.

Adult↗
PubMed1989

Early markers of the renal complications of insulin dependent diabetes mellitus.

We investigated the associations between albuminuria, metabolic control, glomerular filtration, blood pressure, and platelet function in children with insulin dependent diabetes mellitus. The geometric mean (95% tolerance levels) albumin excretion (expressed as the geometric mean albumin to creatinine ratio on two overnight urine collections (UA/UC], in 60 diabetic children was 0.72 (0.80-6.9) mg/mmol, significantly greater than in 45 normal children (geometric mean 0.41 (0.14-1.17]. Mean (SD) glomerular filtration rate, measured by 51Cr edetic acid clearance during constant infusion, was significantly greater in diabetic children (129 (20) ml/min/1.73 m2) compared with normal controls (109 (13]. Mean (SD) renal length for height standard deviation score was +0.25 (1.1); systolic blood pressure standard deviation score was 0.15 (0.65), and diastolic blood pressure was 0.51 (0.82). Spontaneous platelet aggregation, expressed as percentage fall in platelet count in stirred whole blood after 2 minutes was 17.8 (9.2)% in the diabetic compared with 12.3 (7.9)% in normal children. UA/UC correlated with renal length and of the children with UA/UC above the normal range, 70% also had a glomerular filtration rate above the normal range. There was a weak correlation between UA/UC and glycated haemoglobin (HbA1c). All children with spontaneous platelet aggregation above normal had had diabetes for more than seven years. These cross sectional data define some of the early markers and inter-relationships that may be important in the development of nephropathy.

Adolescent↗
PubMed1989

New enzyme immunoassay for detecting total, type I, and type II intrinsic factor antibodies.

A method for the detection of total, type I, and type II intrinsic factor antibodies was devised. The technique comprises a two-site solid phase enzyme linked immunosorbent assay (ELISA), with human intrinsic factor conjugated with horseradish peroxidase as label and attached to polystyrene tubes as solid phase. One conjugation provides sufficient material to assay more than 10,000 patient samples. The label proved stable during the course of this evaluation and was still in use more than 12 months after preparation. When applied to 45 serum samples from cases of pernicious anaemia, intrinsic factor antibodies were shown in 30 (67%). Simplicity, high capacity, low cost and label stability, combined with relatively high clinical sensitivity make the method suitable for cost effective screening of large numbers of samples. Simple modifications to the basic assay reagents permitted type I and type II intrinsic factor antibodies to be differentiated.

Autoantibodies↗