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Biomedical subjects

C A Kim

Publications and source records attributed to C A Kim.

At least 37 records · Page 2Linked to original sources
PubMed1998

Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy.

BACKGROUND: Misoprostol is commonly used to induce abortion in Brazil, and in other countries in South and Central America where abortions are illegal. However, misoprostol is not very effective in inducing abortions, and exposure to the drug in utero can cause abnormalities in the fetus. We aimed to define the common phenotypical effects of exposure to the drug. METHODS: We studied 42 infants from São Paulo, Brazil, who were exposed to misoprostol during the first 3 months of gestation, and then born with congenital abnormalities. We interviewed each of the infants' mothers to find out about misoprostol exposure and dosage. Each infant was physically examined by a geneticist or a neuropaediatrician. FINDINGS: 17 of the infants had equinovarus with cranial-nerve defects. Ten children had equinovarus as part of more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (five cases) and terminal transverse-limb defects (nine cases) with or without Mobius sequence. The most common dose of misoprostol taken was 800 microg (range 200-16000 microg). INTERPRETATION: Deformities attributed to vascular disruption were found in these children. We suggest that the uterine contractions induced by misoprostol cause vascular disruption in the fetus, including brain-stem ischaemia. Information on the effects of taking misoprostol during pregnancy should be made more widely available, to dissuade women from misusing the drug.

Abnormalities, Drug-Induced↗
PubMed1996

A 2.2 A resolution crystal structure of a designed zinc finger protein bound to DNA.

Considerable recent effort has been devoted to the design and selection of sequence-specific DNA binding proteins based on tandem arrays of Cys2His2 zinc finger domains. While the DNA binding properties of these designed proteins have been studied extensively, the structural basis for site-specific binding has not been examined experimentally. Here we report the crystal structure of a complex between a protein comprised of three consensus-sequence-based zinc finger domains and an oligonucleotide corresponding to a favourable DNA binding site. This structure reveals relatively simple modular interactions and structural adaptations that compensate for differences in contact residue side-chain lengths.

Amino Acid Sequence↗
PubMed1995

Serine at position 2 in the DNA recognition helix of a Cys2-His2 zinc finger peptide is not, in general, responsible for base recognition.

The roles of certain amino acids within zinc finger peptides of the Cys2His2 type in determining DNA-binding site specificity were investigated. A variety of three domain peptides designed using a consensus sequence framework were prepared with different potential DNA-contacting residues and tested in a recently developed specificity determination assay. Proteins with recognition helix sequence Q-1S1S2N3L4Q5K6 and QSSDLQK prefer binding subsites 5'-GAA-3' and 5'-(G/T)C(A/G)-3', respectively. Changing the Ser residues in position 2 to Ala in these proteins did not significantly affect the DNA binding site preferences, indicating that Ser residues, which occur frequently in position 2 in known zinc finger proteins are not, in general, responsible for determining binding site preferences. Examination of proteins with recognition helices HSSNLQK and ASSNLQK revealed considerable loss of binding site discrimination throughout the binding subsite. These observations provide further evidence for the importance of residues in positions -1 and 3 in determining DNA binding specificity. Moreover, these results illustrate the effects of changes of one residue in the recognition helix on binding site preferences throughout the recognition subsite.

Amino Acid Sequence↗
PubMed1995

Neuroblastoma in a boy with MCA/MR syndrome, deletion 11q, and duplication 12q.

Deletion 11q23-->qter and duplication 12q23-->qter are described in a boy with neuroblastoma, multiple congenital anomalies, and mental retardation. The patient has clinical manifestations of 11q deletion and 12q duplication syndromes. The possible involvement of the segment 11q23-->24 in the cause of the neuroblastoma is discussed.

Abnormalities, Multiple↗
PubMed1993

Limb deficiency with or without Möbius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy.

Misoprostol, a synthetic analog of prostaglandin, has been widely used in Brazil as an abortifacient. Abortion is illegal in Brazil. An uncertain number of these abortion attempts are unsuccessful and the pregnancy continues. We report on 7 patients whose mothers attempted to abort using this drug in the first trimester of gestation without success. The 7 patients presented with limb defects and in 4 of them a diagnosis of Möbius sequence was made.

Abnormalities, Drug-Induced↗
PubMed1993

Thermodynamic beta-sheet propensities measured using a zinc-finger host peptide.

The three-dimensional structures of proteins reveal that the distribution of amino acids within the major classes of secondary structure is not random but that each amino acid has its own preferred secondary structural arrangements. Propensity scales for residues in alpha-helices have been generated through the use of various host-guest systems. Here we measure the thermodynamic beta-sheet propensities of each of the twenty commonly occurring amino acids. A previously studied zinc-finger peptide was used as the host system in which amino acids were substituted into a guest site, a solvent-exposed position in an antiparallel beta-sheet. As these peptides are unfolded in the absence of bound metal but are folded in their presence, it is assumed that the thermodynamics of metal binding fully reflect peptide-folding energy. A competitive cobalt(II)-binding assay was used to determine these energies with high precision. The relative free energies correlate well with previously derived potential values based on statistical analysis of protein structures. We are therefore able to present a thermodynamic beta-sheet propensity scale for all the commonly occurring amino acids in aqueous solution.

Amino Acid Sequence↗
PubMed1993

Clinical manifestations of leukocyte adhesion deficiency in cattle: 14 cases (1977-1991).

In Holstein cattle, an inherited disease has been recognized recently in which leukocytes lack surface glycoproteins termed beta 2 integrins, which are important in cell adhesion processes. This disease is the homologue of leukocyte adhesion deficiency in human beings and has been termed bovine leukocyte adhesion deficiency. The molecular basis of this disease is failure to produce normal CD18. The gene encoding bovine CD18 and its abnormal mutation have been sequenced, allowing specific diagnosis of the condition by DNA amplification by polymerase chain reaction followed by specific endonuclease digestion. This test was applied to formalin-fixed archival tissues from 18 cattle that had been admitted to the veterinary medical teaching hospital between 1975 and 1991 and that had had persistent and severe neutrophilia. Blood samples were collected from 2 additional cattle, and leukocytes from these samples also were tested. Fourteen cattle were confirmed to have been homozygous for the bovine leukocyte adhesion deficiency gene. Cattle with this condition had ranged in age from 2 weeks to 8 months at admission. They typically had had chronic bacterial infections that had failed to respond to or had recurred after conventional treatment. Consistent findings in these cattle included signs of bronchopneumonia, gingivitis, periodontitis, and peripheral lymphadenopathy. Severe neutrophilia, usually without a left shift, was a hallmark of the disease; consistent clinical biochemical findings included hypoalbuminemia, hyperglobulinemia, and hypoglycemia. This disease is important because it mimics common calfhood diseases such as pneumonia and diarrhea, but is ultimately consistently fatal before adulthood.

Animals↗
PubMed1993

Endourologist at work: laparoscopic placement of drains after nephrectomy.

The exact indications and ideal candidates for laparoscopic nephrectomy are yet to be identified. Occasionally, urologists might drain the renal fossa, depending on the pathogenesis of the renal disease prompting the nephrectomy, as with chronic infection. The authors describe a technique of placing a closed drainage system under full view with insufflation after laparoscopic nephrectomy. No additional stab wounds are necessary.

Drainage↗
PubMed1992

Modulation, in vivo and in vitro, of surface expression of CD18 by bovine neutrophils.

A series of experiments was designed to elucidate some of the factors that may influence surface expression of CD18 by bovine neutrophils. Expression of CD18 was determined by immunofluorescence flow cytometry. Neutrophils recovered from the uterus of cows (n = 9) after intrauterine administration of sterile oyster glycogen solution expressed (mean +/- SD) 123 +/- 21% more CD18 than did circulating neutrophils recovered simultaneously from the same cows (P = 0.003). In 8 cows given 20 mg of dexamethasone IM daily for 3 days, expression of CD18 on blood neutrophils was 29.6 +/- 8% less after treatment than before treatment (P = 0.0078). Neutrophils from 12 cows or bulls exposed to phorbol myristate acetate in vitro increased expression of CD18 by 137 +/- 37% (P = 0.0035). Likewise, exposure of neutrophils from 8 cattle to zymosan-activated bovine plasma increased CD18 exposure by 10.6 +/- 3.8% (P = 0.029). These findings indicate that expression of CD18 by bovine neutrophils is a dynamic system, capable of responding to inflammatory stimuli. Inadvertent activation of neutrophils may be responsible for some of the variance in expression observed when examining large groups of cattle for CD18 expression by neutrophils. The ability of bovine neutrophils to respond rapidly to various stimuli by increasing surface expression of CD18 indicates that a pool of intracellular CD18 may be available for inclusion in the plasmalemma, as has been reported for human neutrophils.

Animals↗
PubMedDate not supplied

AEC syndrome and CHAND syndrome: further evidence of clinical overlapping in the ectodermal dysplasias.

Among the ectodermal dysplasias, there are several examples of overlapping phenotypes in disorders that are considered distinct. We report a 5-year-old boy born to nonconsanguineous parents and presenting with ectodermal dysplasia, ankyloblepharon filiforme adnatum, and bilateral choanal atresia consistent with the diagnosis of AEC syndrome. We compare the findings in our patient with the previous reported cases and discuss the overlapping phenotype of this disorder with CHAND syndrome.

Child, Preschool↗
PubMedDate not supplied

Clinical and radiological aspects in Melnick-Needles syndrome.

Melnick-Needles syndrome is an X-linked dominant bone dysplasia, lethal in males, characterized by a typical facies and characteristic radiological findings: including sclerosis of skull base and mastoids. S-shaped appearance of tibia; cortical irregularities with a ribbon appearance of the ribs. About 48 well-documented cases have been reported, most of them were sporadic. Parental transmission has been published in only 11 kindreds. We are presenting the first Brazilian family with mother-daughter transmission. The proposita presented the typical clinical and radiological features with characteristic facies, severe thoracic cage restriction and pulmonary hypertension. Her mother was more mildly affected.

Adolescent↗