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Biomedical subjects

Y C Chu

Publications and source records attributed to Y C Chu.

13 recordsLinked to original sources
PubMed1992

Clonal evolution in primary 5q-syndrome.

Primary 5q-syndrome is a type of myelodysplastic syndrome characterized by refractory anemia, thrombocytosis, and hypolobulated megakaryocytes. The risk of leukemic transformation is low. A case of 5q- syndrome that occurred in a 42-year-old woman and was complicated by leukemic transformation 7 years after the initial diagnosis is reported. An additional clonal karyotypic anomaly, del(7q), was seen in the leukemic cells. The literature on leukemic and karyotypic evolution of primary 5q- syndrome is reviewed and the implication of karyotypic evolution is discussed.

Acute Disease↗
PubMed1992

The A14 position of insulin tolerates considerable structural alterations with modest effects on the biological behavior of the hormone.

As part of our aim to investigate the contribution of the tyrosine residue found in the 14 position of the A-chain to the biological activity of insulin, we have synthesized six insulin analogues in which the A14 Tyr has been substituted by a variety of amino acid residues. We have selected three hydrophilic and charged residues--glutamic acid, histidine, and lysine--as well as three hydrophobic residues--cycloleucine, cyclohexylalanine, and naphthyl-(1)-alanine--to replace the A14 Tyr. All six analogues exhibit full agonist activity, reaching the same maximum stimulation of lipogenesis as is achieved with porcine insulin. The potency for five of the six analogues, [A14 Glu]-, [A14 His]-, [A14 Lys]-, [A14 cycloleucine]-, and [A14 naphthyl-(1)-alanine]-insulins in receptor binding assays ranges from 40-71% and in stimulation of lipogenesis ranges from 35-120% relative to porcine insulin. In contrast, the potency of the sixth analogue, [A14 cyclohexylalanine]insulin, in both types of assays is less than 1% of the natural hormone. The retention time on reversed-phase high-performance liquid chromatography for the first five analogues is similar to that of bovine insulin, whereas for the sixth analogue, [A14 cyclohexylalanine]insulin, it is approximately 11 min longer than that of the natural hormone. This suggests a profound change in conformation of the latter analogue. Apparently, the A14 position of insulin can tolerate a wide latitude of structural alterations without substantial decrease in potency. This suggests that the A14 position does not participate directly in insulin receptor interaction. Only when a substitution which has the potential to disrupt the conformation of the molecule is made at this position, is the affinity for the receptor, and hence the biological potency, greatly reduced.

Adipose Tissue↗
PubMed1992

Multiple myeloma with tadpolelike cells and rosette formation.

A 65-year-old man with lower back pain was found to have multiple myeloma. Unique findings in the marrow aspirate smears of this patient were tadpolelike plasma cells and cellular rosettes simulating those seen in neuroblastoma. This case documents yet another facet of the broad morphologic spectrum of neoplastic plasma cells in multiple myeloma.

Aged↗
PubMed1992

Diffuse panbronchiolitis: report of a case.

A 33-year-old male presented with a productive cough of yellowish sputum which he had had for several years and progressive dyspnea on exertion that had been present for one year. Physical examination on admission disclosed clubbing of the fingers, diffuse inspiratory crackles and some rhonchi on auscultation. Plain chest film showed diffuse fine nodular lesions in both lungs. Pulmonary function tests demonstrated obstructive ventilatory impairment with a positive bronchodilator response. A CT scan of the chest showed diffuse fine nodular infiltrations in both lung fields. Arterial blood gas analysis of the patient, while breathing room air, revealed mild hypoxemia. The histologic findings of an open lung biopsy specimen were compatible with a diagnosis of diffuse panbronchiolitis. The patient was treated with erythromycin and a bronchodilator, and was regularly followed at the outpatient department. In this report, clinical manifestations, diagnostic criteria and recent advances in the treatment of diffuse panbronchiolitis are discussed.

Adult↗
PubMed1991

Anaplastic large cell Ki-1 lymphoma involving bone marrow: marrow findings and association with reactive hemophagocytosis.

This report describes the bone marrow findings in four patients whose marrow was involved by anaplastic large-cell Ki-1 lymphoma, an uncommon event in this type of lymphoma. In the marrow aspirate smears, the involvement was subtle, and was in the form of isolated large cells with irregular nuclear configuration, coarse chromatin, prominent nucleoli, and basophilic cytoplasm which might be vacuolated. One case showed paradoxically massive involvement in the trephine biopsy taken from the same site as the marrow aspirate. Reactive histiocytic proliferation with hemophagocytosis was also present. Since marrow aspirate or biopsy may be the first pathologic specimen examined in patients having anaplastic large-cell Ki-1 lymphoma, it is important to be able to recognize the small population of neoplastic cells, which should lead to prompt treatment or further investigations as deemed necessary.

Adolescent↗
PubMed1989

Multiple XbaI polymorphisms for carrier detection and prenatal diagnosis of haemophilia A.

Three XbaI restriction fragment length polymorphisms (RFLPs) can be detected using the factor VIII-intron 22 probe (p482.6) in a XbaI-KpnI double digest of genomic DNA. The XbaI (A) site had been reported by Wion et al (1986) to be in intron 22, while the two additional sites. XbaI (B) and XbaI (C), are shown here to be X-linked and close to the XbaI (A) site. The frequencies of heterozygosity for these three sites are 0.49, 0.18 and 0.30 respectively. In 75 females the observed heterozygosity rate for the XbaI (A) site is 0.41 and this increased to 0.57 with the two additional sites. Care should be exercised when interpreting the XbaI RFLPs, since the 1.4 kb XbaI/KpnI fragment and the 4.8 kb XbaI fragment are associated with both positive XbaI (A) and XbaI (B) sites. By the combined use of the multiple XbaI polymorphisms with the BclI site in intron 18, the carrier detection rate would increase to 67%. Four prenatal diagnoses had been performed using the multiple XbaI polymorphisms.

Factor VIII↗
PubMed1987

Possible involvement of the A20-A21 peptide bond in the expression of the biological activity of insulin. 1. [21-Desasparagine,20-cysteinamide-A]insulin and [21-desasparagine,20-cysteine isopropylamide-A]insulin.

The C-terminal region of the A chain of insulin has been shown to play a significant role in the expression of the biological activity of the hormone. To further delineate the contribution of this segment, we have synthesized [21-desasparagine,20-cysteinamide-A]insulin and [21-desasparagine,20-cysteine isopropylamide-A]insulin, in which the C-terminal amino acid residue of the A chain of insulin, asparagine, has been removed and the resulting free carboxyl group of the A20 cysteine residue has been converted to an amide and an isopropylamide, respectively. Both insulin analogues display biological activity, 14-15% for the unsubstituted amide analogue and 20-22% for the isopropylamide analogue, both relative to bovine insulin. In contrast, a [21-desasparagine-A]insulin analogue has been reported to display less than 4% of the activity of the natural hormone [Carpenter, F. (1966) Am. J. Med. 40, 750-758]. The implications of these findings are discussed, and we conclude that the A20-A21 amide bond plays a significant role in the expression of the biological activity of insulin.

Adipose Tissue↗
PubMed1987

Possible involvement of the A20-A21 peptide bond in the expression of the biological activity of insulin. 2. [21-Asparagine diethylamide-A]insulin.

We have synthesized [21-asparagine diethylamide-A]insulin, which differs from the parent molecule in that the free carboxyl group of the C-terminal amino acid residue, asparagine, of the A chain moiety has been converted to a diethylamide group. The analogue displays equivalent potency in receptor binding and biological activity, 48% and 56%, respectively, relative to bovine insulin. In contrast, we have reported previously [Burke, G. T., Chanley, J. D., Okada, Y., Cosmatos, A., Ferderigos, N., & Katsoyannis, P. G. (1980) Biochemistry 19, 4547-4556] that [21-asparaginamide-A]insulin exhibits a divergence in these properties, ca. 60% in receptor binding and ca. 13% in biological activity. The disparity in the biological behavior of these analogues is discussed, and we ascribe the modulation of biological activity independent of receptor binding activity observed between these analogues to the difference in the negativity of the carbonyl oxygen of the A chain moiety C-terminal amino acid residue.

Animals↗
PubMed1987

Possible involvement of the A20-A21 peptide bond in the expression of the biological activity of insulin. 3. [21-Desasparagine,20-cysteine ethylamide-A]insulin and [21-desasparagine,20-cysteine 2,2,2-trifluoroethylamide-A]insulin.

We have synthesized [21-desasparagine,20-cysteine ethylamide-A]insulin and [21-desasparagine,20-cysteine 2,2,2-trifluoroethylamide-A]insulin, which differ from natural insulin in that the C-terminal amino residue of the A chain, asparagine, has been removed and the resulting free carboxyl group of the A20 cysteine residue has been converted to an ethylamide and a trifluoroethylamide group, respectively. [21-Desasparagine,20-cysteine ethylamide-A]insulin displayed equivalent potency in receptor binding and biological activity, ca. 12% and ca. 14%, respectively, relative to bovine insulin. In contrast, [21-desasparagine,20-cysteine 2,2,2-trifluoroethylamide-A]insulin displayed a divergence in these properties, ca. 13% in receptor binding and ca. 6% in biological activity. This disparity is ascribed to a difference in the electronic state of the A20-A21 amide bond in these two analogues. A model is proposed to account for the observation of divergence between receptor binding and biological activity in a number of synthetic insulin analogues and naturally occurring insulins. In this model, changes in the electronic state and/or the orientation of the A20-A21 amide bond can modulate biological activity independently of receptor binding affinity. The A20-A21 amide bond is thus considered as an important element in the "message region" of insulin.

Animals↗
PubMed1987

S-100 protein-positive sinusoidal large cell lymphoma.

A subset of T lymphocytes has recently been reported to express S-100 protein. We report a case of S-100-positive peripheral T-cell lymphoma with a sinusoidal pattern of lymph node involvement. The immunophenotypic profile was T1+, T3+, T4+, T6-, T8-, T11+. The 12-year-old boy presented with thrombocytopenia and splenomegaly and was found to have malignant lymphoma involving the para-aortic lymph nodes, spleen, and bone marrow. The disease ran a rapidly fatal course.

Child↗
PubMedDate not supplied

Large cell lymphoma with initial presentation in the bone marrow.

This report describes 14 cases of large cell lymphoma with initial presentation as marrow involvement in the absence of peripheral lymphadenopathy. The disease affected mainly the middle-aged and elderly, with male predominance. Most patients presented with swinging fever and peripheral blood cytopenia. Reactive hemophagocytic syndrome was a common finding, causing significant morbidity and mortality. Peripheral lymphadenopathy was absent (by case selection), but involvement of the liver, spleen and paraaortic lymph nodes could be demonstrated in some cases. However, in some patients, the involvement was apparently restricted to the bone marrow. Involvement of the bone marrow was often subtle, and could be missed on causal examination. Immunohistochemical studies on eight cases showed that four exhibited a B-cell phenotype, three a T-cell phenotype and one a non-T non-B phenotype. The prognosis was poor, with survival being measured in days to weeks in most patients.

Adolescent↗