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Biomedical subjects

C Smith

Publications and source records attributed to C Smith.

At least 811 records · Page 45Linked to original sources

Bloom syndrome: a single complementation group defines patients of diverse ethnic origin.

Patients of diverse ethnic background were recruited in order to examine whether genetic heterogeneity could be demonstrated in Bloom syndrome (BS). Although most cells from BS patients exhibit high sister-chromatid exchange (SCE), lymphoid cells from some patients exhibit dimorphism for high and low SCE. We addressed the issue of dominance or recessivity of the low-SCE BS phenotype. A high-SCE lymphoblast line, HB1, was mutagenized, and a clone, HB10T, carrying the markers ouabain resistance and thioguanine resistance, was isolated to serve as a fusion parent. Two independent low-SCE BS lines were fused with HB10T, and hybrids were selected in HAT medium supplemented with ouabain. The hybrids, which were tetraploid, exhibited the expected phenotypes when exposed to ouabain and thioguanine. In every case, these hybrids had low SCE levels, establishing dominance of the low-SCE phenotype. The same methodology was also used to assess genetic heterogeneity in BS. A complementation analysis was carried out using high-SCE lymphoblast cell lines derived from BS patients. HB10T was fused with five other high-SCE BS lines. No correction of the high SCE characteristic of BS cells was seen in hybrid lines derived from patients of Ashkenazi Jewish, French-Canadian, Mennonite, or Japanese extraction. Thus, a single gene is responsible for the high-SCE phenotype in BS patients of diverse ethnic origin.

Adolescent↗

Von Hippel-Lindau disease in a large British family: clinicopathological features and recommendations for screening and follow-up.

We describe the clinical and pathological features in nine members of a large British family with von Hippel-Lindau disease. Twenty living family members underwent detailed assessment for features of the disease, including retinal examination and computed tomography of the head and abdomen. The hospital records of three deceased family members were reviewed and detailed information about a fourth was obtained from members of the family. As a result of this study, three asymptomatic family members were found to have features of the disease and all three living affected family members were found to have additional features. Lesions discovered included retinal angiomas requiring treatment in four family members, one asymptomatic renal cell carcinoma and one asymptomatic pancreatic endocrine tumour. We also report the occurrence of a spermatic cord mesenchymal hamartoma in von Hippel-Lindau disease.

Adolescent↗

Crystallization and preliminary X-ray analysis of type B influenza virus neuraminidase complexed with antibody Fab fragments.

Fab fragments from four different monoclonal antibodies have been complexed with influenza B virus neuraminidase (B/Lee/40) and the complexes have been crystallized. Three of the complex crystals are, so far, not suitable for X-ray diffraction studies, but the fourth (B/Lee/40 NA-B1Fab) forms large crystals which diffract X-rays to 3.0 A resolution. The crystals have a space group of F432, a = 441.21 A. Vm calculations show that the asymmetric unit contains two monomeric complexes.

Antibodies, Monoclonal↗

Fine-needle aspiration cytology in the diagnosis of primary breast cancer.

To evaluate the role of fine-needle aspiration (FNA) cytology in the diagnosis of primary breast cancer, we reviewed our experience over a recent 5-year period at Harbor-UCLA Medical Center. A total of 590 aspirates with subsequent follow-up were documented. One hundred thirty-three primary cancers were histologically proved. Of the 133 cancers, 91 (68%) were diagnosed as malignant by aspiration cytologic examination; another 22 (17%) were reported as suspicious. Of the cancers, 8 (6%) had a benign cytologic diagnosis and 12 (9%) had unsatisfactory smears. No cytologic tests positive for malignancy were found to be benign on histologic examination. With an absolute sensitivity of 75% and a specificity of 100%, we conclude that FNA cytologic examination is highly accurate in the diagnosis of breast cancer. With no false-positive studies, the finding of a clearly malignant cytologic condition obviates the need for biopsy before mastectomy.

Adult↗

Heparin-induced thrombocytopenia: laboratory studies.

This report describes studies into the pathophysiology of heparin-induced thrombocytopenia. The IgG fraction from each of nine patients with heparin-induced thrombocytopenia caused heparin-dependent platelet release of radiolabeled serotonin. Both the Fc and the Fab portions of the IgG molecule were required for the platelet reactivity. The platelet release reaction could be inhibited by the Fc portion of normal human or goat IgG, and patient F(ab')2, but not F(ab')2 from healthy controls. These results suggested that the Fab portion of IgG binds to heparin forming an immune complex and the immune complexes initiate the platelet release reaction by binding to the platelet Fc receptors. To directly challenge this hypothesis, we preincubated the serotonin-labeled platelets with the monoclonal antibody against the platelet Fc receptor (IV.3). This monoclonal antibody completely inhibited the release reaction caused by heparin and patient sera, as well as heat aggregated IgG, but did not block collagen or thrombin-induced platelet release. Heparin-dependent platelet release also could be inhibited in vitro by the addition of monocytes and neutrophils, but not by red cells, presumably because the Fc receptors on the phagocytic cells have a higher binding affinity for IgG complexes than do platelets. Platelets from patients with congenital deficiencies of specific glycoproteins Ib and IX (Bernard-Soulier syndrome) and IIb and IIIa (Glanzmann's thrombasthenia) displayed normal heparin-dependent release indicating that the release reaction did not require the participation of these glycoproteins. These studies indicate that heparin-induced thrombocytopenia is an IgG-heparin immune complex disorder involving both the Fab and Fc portion of the IgG molecule.

Antibodies, Monoclonal↗

Splenic reticuloendothelial function after splenectomy, spleen repair, and spleen autotransplantation.

Overwhelming infection after splenectomy remains a problem despite the introduction of vaccine and antimicrobial prophylaxis. To evaluate prospectively various procedures proposed for salvage of the spleen, we measured reticuloendothelial function for two to five years in 51 patients who had initially presented with abdominal trauma and suspected splenic rupture. The mean percentage of pocked erythrocytes and the clearance of antibody-coated autologous erythrocytes in 8 patients who had splenic repair and in 6 who had partial splenectomy were the same as in 11 controls with intraabdominal injury that did not involve the spleen. The mean percentage of pocked erythrocytes remained significantly elevated in 19 patients who had undergone total splenectomy without autotransplantation of splenic tissue. One of seven patients who underwent splenic autotransplantation had a normal level of pocked erythrocytes 18 months after surgery, and a second patient had only a slight elevation at 24 months. The mean (+/- SEM) half-time clearance of labeled erythrocytes was significantly longer in the group that had total splenectomy without autotransplantation (421.1 +/- 74.5 hours) than in the autotransplantation group (91.6 +/- 20.0) or in the controls (5.4 +/- 2.0). We conclude that reticuloendothelial function was better preserved after partial splenectomy and splenic repair than after splenic autotransplantation, but that autotransplantation was superior to total splenectomy and appeared to be safe. Splenic autotransplantation deserves further study in patients who have had splenic trauma when other surgical maneuvers to save the spleen are not possible.

Adolescent↗

Prevalence of HPV DNA and viral copy numbers in cervical scrapes from women with normal and abnormal cervices.

Cervical scrapes were obtained from 215 women with cytologically normal cervices and 74 women with cervical intraepithelial neoplasia (CIN) and probed for HPV 6, 11, 16, and 18 by dot-blot hybridization. Viral copy numbers were determined by densitometric scanning of autoradiographs. The prevalence of HPV DNA in women with normal smears was as follows: 23 per cent of women attending a Family Planning Clinic (FPC), 16 per cent of women attending a Sexually Transmitted Diseases (STD) clinic, and 48 per cent of women attending a laser follow-up clinic after treatment of CIN. Ten per cent of women with normal cervices harboured HPV 16. Viral copy numbers ranged from 1300 to 52,800 genome equivalents per cell. Twenty-seven HPV-positive women with normal smears (including four patients infected with HPV 16) were followed for up to 3 years. None developed CIN irrespective of copy number. Our results show that HPV is present in normal cervices in the absence of CIN. Copy number has no relation to the development of CIN and factors other than the amount of HPV DNA may trigger the neoplastic process.

Adolescent↗

Adenocarcinoma of the canine prostate: immunohistochemical examination for secretory antigens.

Thirty-one canine adenocarcinomas of prostatic origin were examined immunohistochemically with antibodies generated against three prostate-specific antigens by using a peroxidase-antiperoxidase technique. Primary antibodies included two generated with human prostatic antigens (PSA, PSAP) and one generated with a canine prostatic antigen (CPSP). Eight of 31 adenocarcinomas were positive with CPSP, two were positive with PSA, and three were PSAP positive. Normal and hyperplastic canine prostatic epithelium was strongly positive with all three markers. These results contrast with those in human studies in which PSA and PSAP stain normal and neoplastic epithelium with comparable intensity in all but the most anaplastic tumors.

Adenocarcinoma↗

Efficacy of postevacuation view after double-contrast barium enema.

A single postevacuation view was obtained in each of 100 consecutive patients undergoing double-contrast barium enema to determine the efficacy of the routine use of this view. This view was unequivocally helpful only when complete appendiceal filling was desired (1% of our series). Otherwise, this view was either noncontributory (95%), of doubtful assistance (3%), or misleading (1%). Therefore, the postevacuation view should not be obtained routinely.

Barium Sulfate↗

Source of prenatal care and infant birth weight: the case of a North Carolina county.

The impact of a comprehensive prenatal care program on the birth weights of infants born to low-income women is assessed. Women receiving care through the prenatal program of a large county public health department were compared to pregnant Medicaid-eligible women in the same county, who received prenatal care primarily from private-practice physicians. The percentage of low birth weight was 8.3 for the health department women compared with 19.3 for the Medicaid women. After differences between the two groups in race, marital status, participation in the Special Supplemental Food Program for Women, Infants, and Children (WIC), quantity of prenatal care, and other risk factors were statistically controlled, the chance of a Medicaid woman having a low-weight birth was still more than twice as great (p = 0.007). A case-management approach and greater use of services ancillary to basic obstetric medical care appear to contribute to the better birth weight outcomes in the health department.

Birth Weight↗

Tracheomalacia: an experimental animal model for a new surgical approach.

Tracheomalacia was created by removing the posterior 50% of the circumference of eight cartilage rings (5-6 cm in length) from the intrathoracic trachea in each of 12 piglets while leaving the mucosa intact. In 6 animals an autologous, free tibial periosteal graft was applied over the defect (graft group). The remaining 6 piglets served as the control group. In all animals, a silastic stent was left in the trachea for 2 weeks to prevent immediate tracheal collapse. The presence of tracheomalacia was assessed 6-8 weeks after surgery. At bronchoscopy total tracheal collapse during coughing occurred only in the controls. As the animals went from quiet breathing to coughing, mean intrathoracic pressure increased from 5 to 80 cm H2O in both groups, and average sagittal tracheal diameter decreased by 10% in the graft group and 71% in the controls. During coughing, mean resistance to airflow across the defect increased by 0.005 +/- 0.002 cm H2O/liter/min in the graft group, by 0.083 +/- 0.96 cm H2O/liter/min in the controls (P less than 0.005), and by 0.027 cm H2O/liter/min at the same tracheal level in two normal pigs. At sacrifice 12 weeks postoperatively, bone and collagenized fibrous tissue had been produced by all grafts, without evidence of stricture. This study shows that experimentally induced tracheomalacia can be treated successfully by the application of an autologous periosteal tibial graft, which becomes incorporated into the weakened tracheal wall.

Airway Resistance↗

Inhibition of SK cell activity in frogs by certain drugs and sugars.

We present similarities between mammalian natural killer (NK) cells and (anuran amphibian) frog spontaneous killer (SK) cells. A cytotoxic assay utilizing allogeneic erythrocytes as target cells was used and lysis assessed by measuring release of hemoglobin. SK effector cells, just as mammalian NK cells, are not sensitive to cycloheximide nor most simple sugars (50 mM glucose, glucose-6-phosphate, galactose, fucose, mannose). However, SK activity is inhibited by chloroquine, colchicine and mannose-6-phosphate. When SK cells were co-incubated with mammalian tumor cells, they were able to lyse only the NK-sensitive target YAC-1, but not other mammalian tumor cell targets including K562, Molt-4, Raji, P815 and EL4. Lysis of YAC-1 cells was also inhibited by colchicine and chloroquine. These results allow speculation on the evolution of cell mediated cytotoxicity since natural cytotoxic cells are present in ectothermic vertebrates.

Animals↗