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Biomedical subjects

K Chun

Publications and source records attributed to K Chun.

At least 19 recordsLinked to original sources
PubMed1999

Achondroplasia-hypochondroplasia complex in a newborn infant.

We describe the case of an 8-month-old girl with achondroplasia-hypochondroplasia complex. The diagnosis was suggested antenatally when obstetrical ultrasonography at 27 weeks of gestation showed short limbs, small chest, and macrocephaly. The father has achondroplasia due to the common G1138A (G380R) mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, while the mother has hypochondroplasia due to the C1620G (N450K) mutation in the FGFR3 gene. Neither had had genetic counseling or molecular testing prior to the pregnancy. Antenatal ultrasound study at 29 weeks of gestation showed a large head, very short limbs, and a small chest; the findings were more severe than in achondroplasia or hypochondroplasia alone. The patient was born by cesarean section at 37 weeks of gestation and had rhizomelic shortness of limbs with excess skin creases, large head, and small chest, diagnostic of achondroplasia. Radiographs showed shortness of the long bones and flaring of the metaphyses. She had mild hypoplasia of lungs. Molecular testing showed both the G1138A and the C1620G mutations in FGFR3, confirming the diagnosis of achondroplasia-hypochondroplasia complex. At 8 months, she has disproportionate shortness of the long bones and a large head with frontal bossing and a depressed nasal bridge. Her chest remains small, and she is on home oxygen at times of respiratory stress. She has a large gibbus. She is delayed in her motor development and has significant head lag. To our knowledge, there is only one previously published report of achondroplasia-hypochondroplasia complex.

Abnormalities, Multiple↗
PubMed1999

Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.

We report on a male newborn infant, a compound carrier of heterozygous mutations in the FGFR3 gene causing achondroplasia and hypochondroplasia. The mother has achondroplasia and carries the common G1138 (G380R) mutation in the FGFR3 gene; the father has hypochondroplasia due to the C1620A (N540K) mutation in the same gene. The fetus was found to carry both mutations diagnosed prenatally by amniocentesis at 17.6 weeks of gestation, following maternal serum screening which showed an increased risk for Down syndrome (1:337). Detailed fetal ultrasound studies showed a large head, short limbs, and a small chest at 22 weeks of gestation. The changes were more severe than those of either achondroplasia or hypochondroplasia. The patient was born by cesarean section at 38 weeks of gestation and had rhizomelic shortness of the upper and lower limbs with excess skin folds, large head, enlarged fontanelles, frontal bossing, lumbar gibbus, trident position of the fingers, and a narrow chest with a horizontal line of demarcation at the narrowest area of the chest. Skeletal radiographs showed shortness of the long bones and flare of metaphyses. He had respiratory difficulties and was treated with nasal prongs. Seizures developed on day 2 of life and recurred on day 9 and responded to treatment with phenobarbital. Brain computed tomographic scan showed possible grey matter heterotopia, partial agenesis of the corpus callosum, and cortical dysplasia. To our knowledge, there are only two previously published cases of compound heterozygous achondroplasia-hypochondroplasia patients. The diagnosis was confirmed by DNA mutation analysis of the FGFR3 gene in both cases.

Abnormalities, Multiple↗
PubMed1998

FGFR2 mutation associated with clinical manifestations consistent with Antley-Bixler syndrome.

The Antley-Bixler syndrome (ABS) is a rare syndrome with synostosis of cranial sutures and elbow joints as minimal diagnostic criteria. The inheritance has been suggested to be autosomal recessive based on two families with sib recurrence with both sexes being affected, and two cases born to consanguineous parents. We report the first case of ABS associated with an apparent dominant de novo mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. The patient was found to be heterozygous for a C-->G transversion at nucleotide 1064, which predicts a Ser351Cys amino acid substitution in the IgIII domain of FGFR2. Apart from the craniosynostosis and elbow ankylosis, our patient also presented with severe spinal dysraphism, the first report of such a finding in association with ABS. This suggests that FGFR2 is expressed as early as the fourth week of embryogenesis when somite formation occurs. We propose that the Antley-Bixler syndrome is an autosomal dominant condition with possible gonadal mosaicism. Alternatively, there may be two types of ABS: an autosomal dominant form and an autosomal recessive form. In light of our findings, FGFR mutations should be looked for in other craniosynostosis patients with elbow synostosis.

Abnormalities, Multiple↗
PubMed1998

Expression of normal and mutant pyruvate dehydrogenase complex E1 alpha cDNAs in cultured human lymphoblasts.

Transfection of PDH E1 alpha cDNAs into human normal (3781) and PDH-deficient (4787) lymphoblast cell lines was performed to study the expression of different E1 alpha cDNAs. Transfection of normal human E1 alpha cDNA into a severely PDH-deficient cell line with 10% residual activity resulted in a fivefold increase in residual PDH complex activity. Transfection of the normal cDNA into the normal cell line did not affect the residual enzyme activity. Transfection of three known human PDH E1 alpha mutations (A875T, C787G, and a 13-bp insertion at nucleotide 981) into the normal cell line resulted in a decrease of PDH complex activity. Expression of these same mutations in the deficient cell line resulted in an increase of PDH complex activity, with the C787G mutation causing the greatest increase in enzyme activity. The increase in activity seen with A875T expressed in the mutant cell line suggested that interallelic complementation had occurred.

Cells, Cultured↗
PubMed1997

Scrotoschisis associated with contralateral meconium periorchitis.

Scrotoschisis, a congenital defect of the scrotal wall associated with extracorporeal testicular ectopy, has been previously reported only twice. Meconium periorchitis is another rare scrotal anomaly indicative of an antenatally healed gastrointestinal perforation. The authors present a third case of scrotoschisis and the first associated with meconium periorchitis. Several hours after birth of an otherwise-normal term baby boy, a scrotal exploration was performed with orchidopexy and primary closure of the scrotal wall defect. At 4 months of age the baby underwent a contralateral inguino-scrotal exploration with excision of a paratesticular mass of calcified meconium. The role of a normally developed scrotum in testicular descent and causes of calcified scrotal masses in infants are discussed.

Humans↗
PubMed1996

Naive murine neonatal T cells undergo apoptosis in response to primary stimulation.

The cellular mechanisms controlling deficient immune responses in newborn animals are not well understood. Our earlier studies showed that developmental regulation of Th cell activity may be one of the major causes of immunodeficiency in neonatal animals. Naive murine neonatal T cells showed poor Th1 activity but robust Th2 activity in response to primary stimulation in vitro. Although they produced high levels of IL-4, neonatal T cells proliferated poorly, suggesting that neonatal T cell survival in primary cultures may be limited. We show here that, unlike adult T cells, naive neonatal T cells undergo apoptosis in response to primary TCR-mediated stimulation. Ligation of the TCR alone, in the absence of accessory cell costimulation, is sufficient to induce apoptosis. Moreover, CD4+ and CD8+ T cells show equivalent levels of apoptosis. Lastly, this apoptosis can be prevented by the addition of excess IL-2 or by conditions promoting a high level of IL-2 production (TCR-independent stimulation, anti-CD28 mAb, or exogenous IL-6) by neonatal T cells. However, IL-2 alone is not sufficient to support functional rescue from apoptosis; only IL-6 supports the ability of these cells both to survive and to mount vigorous secondary responses. The identification of conditions allowing functional rescue from apoptosis in vitro has important implications for enhancing vaccine responsiveness in vivo.

Animals↗
PubMed1996

Disorders of pyruvate carboxylase and the pyruvate dehydrogenase complex.

The most common defect associated with deficiency of the pyruvate dehydrogenase (PDH) complex occurs in the E1 component, specifically due to mutations in the X-linked E1 alpha gene. Clinical sequelae of these mutations, which range from severe neonatal lactic acidosis to carbohydrate-sensitive ataxia, can be different in males and females depending on the nature of the mutation and, in the case of females, on the X-inactivation pattern in different tissues. Males have a high representation of missense mutations among the patient cohort, while females are much more likely to have DNA rearrangements, particularly toward the 3' end of the coding sequence of the gene. Missplicing mutations involving exon 6 deletion have been reported, as has a missense mutation conferring true thiamin-responsiveness of the enzyme and the patient's clinical symptoms. Pyruvate carboxylase deficiency, on the other hand, is a true autosomal recessive disease, though it has high occurrences in particular ethnic groups, especially in Algonkian-speaking Amerindians and in Arabs. In the former group the defect is a simple type in which material cross-reactive to pyruvate carboxylase antibody is present in cultured cells (CRM+ve). In the latter group, cross-reacting material is rarely present (CRM-ve). The CRM+ve patients can survive into teenage years with careful supervision, while the CRM-ve patients have complications due to hyperammonaemia and dysfunction of the urea cycle and rarely survive beyond 3 months of life.

Amino Acid Sequence↗
PubMed1996

Fibro-osseous pseudotumor of the digit: a comparison to myositis ossificans by light microscopy and immunohistochemical methods.

Fibro-osseous pseudotumor of the digit is an unusual cutaneous process characterized histologically by a fibroblastic proliferation admixed with reactive/metaplastic osteoid formation. The osteoid formation can be florid and immature, mimicking the appearance of malignant osteoid-forming neoplasms. Fibro-osseous pseudotumor of the digit has histologic and clinical features in common with myositis ossificans. This has led many to consider the two to be synonymous. We studied three cases of fibro-osseous pseudotumor, compared to five cases of myositis ossificans, using routine light microscopy and a battery of immunohistochemical stains. Both entities displayed a "zoning" pattern of immature spindled areas admixed with more mature areas having osteoid metaplasia. This was more pronounced in myositis ossificans. In each lesion, the spindle cells stained positively for vimentin and actin. CD34 and Factor VIII highlighted the vasculature. No stromal staining for MAK-6 (cytokeratin) or S-100 was identified. Ki-67, a proliferation marker, showed positive staining of the stromal cells in both lesions, which was strongest in the immature spindled areas. The immunohistochemical and histologic similarities of the lesions support fibro-osseous pseudotumor of the digit being a cutaneous variant of myositis ossificans.

Adolescent↗
PubMed1995

Gastroschisis: a simple technique for staged silo closure.

In conjunction with the Neonatology Department at Loma Linda University Children's Hospital, a new protocol has evolved for the management of infants with gastroschisis, which obviates both risks associated with primary and staged silo closure. After stabilization of the infant in the neonatal intensive care unit, under sterile conditions, a 5- or 7-cm SILASTIC silo with a spring-loaded ring is placed over the exposed viscera, under the fascial defect. No sutures are required. A fentanyl drip is given, and the bowel is gradually reduced over the next few days. The transparent material of the silo allows for continuous monitoring of the condition of the bowel. Second-stage closure in the operating room is performed using a purse-string suture in the fascia to create a pseudoumbilicus. From October 1992 to April 1994 the authors managed 10 infants using this protocol. The results are compared with those of infants with gastroschisis treated at the same institution between August 1982 and June 1993. Outcome parameters to be compared include time until closure, time on ventilation, days of total parenteral nutrition, time until start of oral feeding, time until toleration of full-volume oral feeding, and time until discharge. The authors conclude that silo closure in the neonatal intensive care unit is simple, quick, and effective. It eliminates multiple trips to the operating room, allows the natural accommodation of the bowel into the abdominal cavity with little edema and minimal vascular compromise, and has become the authors' treatment of choice for infants with gastroschisis.

Abdominal Muscles↗
PubMed1995

Nevus sebaceus: clinical outcome and considerations for prophylactic excision.

BACKGROUND AND OBJECTIVE: Nevus sebaceus is a hamartoma of the skin with the potential to develop benign and malignant neoplasms. Prophylactic surgical excision has been advocated, usually before puberty, to prevent their occurrence; however, it is the clinical impression of the authors that the development of cutaneous neoplasms is infrequent and, if they develop, they are usually benign and nonaggressive. Our objective was to investigate the clinical outcome and histopathologic findings of every single nevus sebaceus that had been excised in our institution in a five-year period. METHODS: Two hundred and twenty-five consecutive cases, coded as nevus sebaceus corresponding to 175 patients were submitted to our institution between September 1987 and May 1992, and were identified among a total of 64,827 specimens. All cases were reviewed histopathologically and clinical information was obtained from the records. Specimens from 10 patients were excluded. RESULTS: A total of nine benign neoplasms (5.4%) were identified in the 165 patients. Three patients were in their second decade of life, two in their third, two in the fifth and two in the sixth. There were five trichoblastomas, three specimens of syringocystadenoma papilliferum, and one aprocrine cystadenoma. No malignant neoplasms were found. Six of the tumors were removed either for prophylactic or cosmetic reasons and in only three cases were the neoplasms suspected clinically and excised. CONCLUSIONS: If this same tendency prevails in other prospective studies, we strongly believe that prophylactic excision of all nevus sebaceus is not warranted. Excision should be recommended only when benign or malignant neoplasms are clinically suspected or for cosmetic considerations.

Adolescent↗
PubMed1995

Caffeine-halothane accuracy in MH testing.

The accuracy and stability of caffeine and halothane concentrations in liquid Krebs medium were examined. Caffeine-Krebs Ringer's solution in incremental concentrations from 0.25 to 10 mM (N = 8 for each concentration) was serially assayed over a three-year period. Storage was at 4 degrees C. For serial testing of halothane during a five month period, halothane 1% or 3% in carbogen was bubbled through a Krebs solution, contained in muscle baths, either using a roller pump (to eliminate vaporizer back pressure) or using carbogen at a line pressure of 4-6 lbs/in2 (27-41 kPa). Halothane in Krebs was assayed by high pressure liquid chromatography. Caffeine concentrations did not vary for 20 weeks. From then, through 60 weeks, concentrations less than 2 mM steadily diminished; after that, through 156 weeks, only 4, 8, and 10 mM were stable. When compared to the halothane concentration in gas entering the muscle baths, halothane concentration in Krebs was predictable regardless of method delivery, as long as a gas analyzer indicated the proper concentration. We conclude that caffeine solutions are stable for 20 weeks when refrigerated, and for three years at concentrations 4 mM or greater.

Caffeine↗
PubMed1995

Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase: exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex.

Human pyruvate dehydrogenase (PDH)-complex deficiency is an inborn error of metabolism that is extremely heterogeneous in its presentation and clinical course. In a study of 14 patients (7 females and 7 males), we have found a mutation in the coding region of the E1 alpha gene in all 14 patients. Two female patients had the same 7-bp deletion at nt 927; another female patient had a 3-bp deletion at nt 931. Another female patient was found to have a deletion of exon 6 in her cDNA. Two other female patients were found to have insertions, one of 13 bp at nt 981 and one of 46 bp at nucleotide 1078. Two male patients were found to have a 4-bp insertion at nucleotide 1163. The remaining six patients all had missense mutations. A male patient and a female patient both had an A1133G mutation. The other missense mutations were C214T, C615A, and C787G (two patients). Five of these mutations are novel mutations, five have been previously reported in other patients, and two were published observations in other patients in an E1 alpha-mutation summary. In the four cases where parent DNA was available, only one mother was found to be a carrier of the same mutation as her child.

Base Sequence↗
PubMed1994

Thumb duplication, 66 years' experience--a review of surgical complications.

Fifty-four supernumerary thumbs excisions were followed for an average of 9 years for results of their surgical management, which consisted of simple excision (16 patients), reconstructive procedures (33 patients), or central wedge resections (5 patients). Half of all simple excisions and reconstructive procedures gave unacceptable results, most were salvaged. These were primarily joint deviations, joint instabilities, and bony prominences. All of our central wedge resections gave unacceptable results that were not salvageable--short, stiff, fat thumbs with nail deformities. We feel this procedure should probably be reserved for cases where both digits of the supernumerary thumbs are severely hypoplastic.

Adolescent↗
PubMed1994

Microcirculatory failure determines lethal hepatocyte injury in ischemic/reperfused rat livers.

The contribution of microcirculatory failure to ischemia/reperfusion injury in isolated perfused rat livers was investigated using intravital epifluorescence videomicroscopy. The degree of microvascular shut-down during reperfusion was modulated by the reperfusion conditions: flow-controlled (10 ml/min), in which microcirculatory failure is minimized by maintenance of constant flow through the liver, and pressure-controlled, in which microvascular shut-down is allowed to occur. Livers underwent 60 min of ischemia, 90 min of ischemia, or no ischemia (control). Perfused sinusoids and dead hepatocytes were quantified in 10 standardized microscopic fields (9000 microns2) per liver during off-line video playback. With flow-controlled reperfusion, microvascular (sinusoid) shut-down was largely avoided; a maximum of 21% of the sinusoids failed to conduct flow. Pressure-controlled reperfusion, however, resulted in early and severe shut-down. A significant decrease of approximately 20-30% was found after 60 min of ischemia and 30 min of reperfusion, while, after 90-min ischemia and 90-min reperfusion, 90% of the sinusoids failed to conduct flow. The appearance of dead hepatocytes correlated well with the number of perfused sinusoids (r = -0.78 for flow controlled, r = -0.97 for pressure-controlled). Only an occasional dead hepatocyte was observed with control perfusion, while up to 50% stained with propidium iodide following 90-min ischemia and 90-min reperfusion under pressure-controlled conditions. These results indicate that loss of sinusoidal flow can be ameliorated by flow-controlled reperfusion; moreover, hepatocyte necrosis during reperfusion is highly dependent upon the integrity of the microcirculation.

Animals↗