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Biomedical subjects

P T Ho

Publications and source records attributed to P T Ho.

At least 19 recordsLinked to original sources
PubMed2004

Photonic logic NOR gate based on two symmetric microring resonators.

We demonstrate an all-optical NOR logic gate based on symmetric GaAs-AlGaAs microring resonators whose resonances are closely matched. Two input pump data streams are tuned close to one resonance of the symmetric microrings to switch a probe beam tuned to another resonance by two-photon absorption. The switching energy of the gate is 20 pJ/pulse, and the switching window is 40 ps, limited by the carrier lifetime. The use of two rings provides for better cascading in photonic logic circuits because of the higher number of available ports.

Journal Article↗
PubMed2004

Enhanced linear and nonlinear optical phase response of AlGaAs microring resonators.

We have constructed and characterized several optical microring resonators with scale sizes of the order of 10 microm. These devices are intended to serve as building blocks for engineerable linear and nonlinear photonic media. Light is guided vertically by an epitaxially grown structure and transversely by deeply etched air-clad sidewalls. We report on the spectral phase transfer characteristics of such resonators. We also report the observation of a pi-rad Kerr nonlinear phase shift accumulated in a single compact ring resonator evidenced by all-optical switching between output ports of a resonator-enhanced Mach-Zehnder interferometer.

Journal Article↗
PubMed2001

Spherical episodic ejection of material from a young star.

The exact processes by which interstellar matter condenses to form young stars are of great interest, in part because they bear on the formation of planets like our own from the material that fails to become part of the star. Theoretical models suggest that ejection of gas during early phases of stellar evolution is a key mechanism for removing excess angular momentum, thereby allowing material to drift inwards towards the star through an accretion disk. Such ejections also limit the mass that can be accumulated by the stellar core. To date, these ejections have been observed to be bipolar and highly collimated, in agreement with theory. Here we report observations at very high angular resolution of the proper motions of an arc of water-vapour masers near a very young, massive star in Cepheus. We find that the arc of masers can be fitted to a circle with an accuracy of one part in a thousand, and that the structure is expanding. Only a sphere will always produce a circle in projection, so our observations strongly suggest that the perfectly spherical ejection of material from this star took place about 33 years earlier. The spherical symmetry of the ejecta and its episodic nature are very surprising in the light of present theories.

Journal Article↗
PubMed1999

Pervasive developmental delay in children presenting as possible hearing loss.

OBJECTIVE/HYPOTHESIS: Children who fail to develop adequate language skills and/or appropriate social skills by age 2 years often are referred to the department of otolaryngology for otolaryngologic examination and evaluation of possible hearing deficits. Discovering a gross disparity between hearing function and language ability often uncovers an underlying developmental disorder satisfying criteria for diagnosis on the spectrum of autism and pervasive developmental delay (PDD). The otolaryngologist has a unique opportunity to identify these autistic children and initiate their evaluation and management. STUDY DESIGN: Retrospective review. METHODS: Review of charts of children referred over the past 4 years to the Department of Otolaryngology for possible hearing loss identified 15 children who were later diagnosed with PDD. RESULTS: Fifteen children initially referred for hearing evaluation were subsequently identified with a diagnosis of PDD. Males outnumbered females 4 to 1, with the average age of referral being 2 years. One third of the patients displayed middle ear disease that improved with PE tube placement. One third of the patients showed brainstem conduction dysfunction on auditory brainstem evoked response testing. CONCLUSIONS: Children with developmental delays, especially higher functioning ones, may present with a myriad of language and communication deficits that are often mistakenly attributed to hearing loss. Otolaryngologists and audiologists can assist in their early identification and appropriate referral for therapy.

Audiometry, Pure-Tone↗
PubMed1998

Cancer recurrences and secondary primary cancers after use of antihistamines or antidepressants.

OBJECTIVES: Reports in the scientific literature have described accelerated tumor growth in association with antidepressant and antihistamine exposure in experimental rodent cancer models. This study was designed to determine whether exposure to prescription antidepressants or antihistamines is associated with tumor growth in humans. METHODS: Two nested case-control studies were conducted with a cohort of 1467 patients with breast cancer, colon cancer, or melanoma diagnosed between 1988 and 1994. Eligible patients included 95 with a cancer recurrence and 78 with a second primary lesion diagnosed during the follow-up period. Five control subjects were matched to each case patient according to cancer site, stage, and follow-up time. Conditional logistic regression was used to compare risk for tumor recurrence or occurrence of a second primary tumor among patients using antidepressants or antihistamines with risk among unexposed patients. RESULTS: For a cohort of patients who were predominantly female (78%), with breast cancer (57%) and with a tumor in situ or with localized disease (79%), the average age was 62 years at cancer diagnosis and average duration of follow-up period was 2.2 years. Use of antidepressants or antihistamines was unrelated to risk for tumor recurrence (odds ratio, 0.97; 95% confidence interval, 0.52 to 1.78) or second primary tumors (odds ratio, 0.94; 95% confidence interval, 0.50 to 1.77). CONCLUSION: Typical use of antidepressant or antihistamine drugs did not increase risk for recurrent or second primary tumors among patients with cancer.

Adult↗
PubMed1997

Antisense oligonucleotides as therapeutics for malignant diseases.

The continued progress in our understanding of the biology of neoplasia and in the identification, cloning, and sequencing of genes critical to tumor cell function permits the exploitation of this information to develop specific agents that may directly modulate the function of these genes or their protein products. Antisense oligonucleotides are being investigated as a potential therapeutic modality that takes direct advantage of molecular sequencing. The antisense approach uses short oligonucleotides designed to hybridize to a target mRNA transcript through Watson-Crick base pairing. The formation of this oligonucleotide: RNA heteroduplex results in mRNA inactivation and consequent inhibition of synthesis of the protein product. A fundamental attraction of the antisense approach is that this method potentially may be applied to any gene product, in theory, for the treatment of malignant and non-malignant diseases. However, this simple and attractive model has proven to be much more complex in practice. A number of important challenges in the preclinical development of antisense oligonucleotides have been identified, including stability, sequence length, cellular uptake, target sequence selection, appropriate negative controls, oligonucleotide: protein interactions, and cost of manufacture. Although the biological activity of an oligonucleotide against its molecular target is theoretically sequence-dependent, the animal pharmacokinetics and toxicology of phosphorothioate analogues directed against vastly disparate gene products appear relatively non-sequence-specific. In oncology, a number of clinical trials have been initiated with antisense oligonucleotides directed against molecular targets including: p53; bcl-2; raf kinase; protein kinase C-alpha; c-myb. The experience gained from these early clinical trials will be applicable to the next generation of antisense agents in development. These may include molecules with novel backbones or other structural modifications, chimeric oligonucleotides, or peptide nucleic acids. Continued progress in this arena will require that many of the preclinical challenges confronting antisense development are satisfactory resolved.

Animals↗
PubMed1997

Promising new agents under development by the Division of Cancer Treatment, Diagnosis, and Centers of the National Cancer Institute.

The Division of Cancer Treatment, Diagnosis and Centers of the National Cancer Institute (NCI) has a large program in clinical cancer therapeutics development. It currently holds investigational new drug applications for nearly 200 agents with which it sponsors clinical trials. In addition, it has a major preclinical development program. With the tremendous advances in our understanding of molecular and tumor biology during the past decade, the NCI's portfolio of agents has expanded beyond classical cytotoxic agents to include a wide variety of new molecular and therapeutic targets. In addition to agents with more conventional mechanisms of action, the NCI has targeted therapeutics programs that focus on tumor vasculature, cell cycle control and cell signaling, mechanisms of apoptosis, invasion and metastasis, and immunological recognition and response. Each of these focused areas includes agents of different classes and modes of action that are all directed at the target of interest. The scope of the NCI's program allows it to respond to incorporate promising new agents or targets as they arise and to prioritize them for use of preclinical and clinical resources. Agents in development through the NCI are derived from a number of diverse sources including its own screening efforts, academia, and numerous collaborations with the pharmaceutical and biotechnology industries. NCI works closely with collaborators to ensure complementary, non-duplicative clinical development and attempts to ensure that the full potential of promising agents is explored. A number of compounds in early clinical development or about to enter the clinic are discussed briefly in this manuscript.

Antineoplastic Agents↗
PubMed1996

Pediatric drug development: a perspective from the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI).

Well-designed and carefully conducted pediatric phase 1 trials are critical to the process of evaluating new agents for potential benefit in children with cancer, and the National Cancer Institute (NCI) has for a number of years sponsored pediatric phase I trials. The development of new agents for children with cancer differs in important ways from drug development for adults with cancer, primarily necessitated by the smaller number of children eligible for phase I trials in comparison to adults. Pediatric drug development is characterized by a greater need to prioritize new agents for evaluation, since many more agents can be evaluated in adults than can be evaluated in children. Pediatric phase I trials are also commonly conducted as multi-institutional collaborations, since most single institutions do not have enough eligible patients to complete phase I trials within a reasonable time. In addition, pediatric phase I trials begin at doses close to the adult maximum tolerated dose, thereby minimizing the number of patients required to complete pediatric phase I trials. While pediatric phase I trials have traditionally evaluated conventional cytotoxic agents, new classes of agents with distinctive mechanisms of action are entering clinical evaluation. These agents target specific cellular proteins (e.g., protein tyrosine kinases, protein kinase C isoforms, enzymes involved in controlling progression through the cell cycle). Determining whether these agents with specificity for critical cellular proteins will be effective anti-cancer agents will be an important objective of pediatric clinical investigations in the coming years.

Antineoplastic Agents↗
PubMed1995

A prospective evaluation of ifosfamide-related nephrotoxicity in children and young adults.

BACKGROUND: Ifosfamide has been associated with proximal renal tubular dysfunction resembling Fanconi-like syndrome and leading to rickets in young children. The characteristic manifestations of this nephrotoxicity include phosphaturia and hypophosphatemia, glycosuria, aminoaciduria, renal tubular acidosis, and urinary loss of low molecular weight serum proteins. However, the relationship between acute ifosfamide nephrotoxicity, which is frequently subclinical, and long term renal damage is unclear. In this prospective study, the laboratory features of ifosfamide-induced acute nephrotoxicity were characterized further and correlated with the development of chronic nephropathy. METHODS: The renal function of newly diagnosed children and young adults with high risk sarcomas was followed during therapy with a high dose ifosfamide-containing regimen. Serum and urine were collected regularly immediately before and after 5-day cycles of ifosfamide throughout treatment for determination of the fractional excretion of electrolytes (sodium, potassium, phosphate, magnesium, calcium) and glucose and urinary excretion of amino acids and beta 2-microglobulin. RESULTS: Significant changes in the renal threshold of phosphate excretion, the fractional excretion of calcium and glucose, and the urinary excretion of beta 2-microglobulin were observed when comparing pretreatment values with those at the end of a 5-day treatment cycle. The median renal threshold of phosphate excretion decreased from 1.22 to 0.82 mmol/L (P < 0.0001). The median fractional excretions of calcium and glucose increased from 1.05% to 1.68% (P < 0.0001) and 0.05% to 0.08% (P = 0.0006), respectively. Beta 2-microglobulin excretion increased by 70-fold from 0.02 to 1.42 mg/mmol (P < 0.0001). Except for glucose and beta 2-microglobulin excretion, renal parameters returned to baseline before the next ifosfamide treatment cycle. Acute aminoaciduria was observed in 21 of 23 patients. Chronic nephrotoxicity, as defined by the development of a Fanconi-like syndrome or chronic tubular electrolyte loss requiring oral supplementation, developed in the three patients with the highest urinary excretion of beta 2-microglobulin after ifosfamide therapy. CONCLUSIONS: Prospectively, high dose ifosfamide was associated with a 4% incidence of Fanconi-like syndrome; however, evidence of acute reversible subclinical nephrotoxicity was observed for all patients. Severe beta 2-microglobulinuria appeared to be a prognostic laboratory indicator for the development of chronic nephrotoxicity.

Adolescent↗
PubMed1994

A high-resolution image of atomic hydrogen in the M81 group of galaxies.

It has long been recognized that interactions between galaxies are important in determining their evolution. The distribution of gas--out of which new stars are formed--is strongly affected; in particular, gas may be concentrated near the nucleus, leading to a burst of star formation. Here we present a map of atomic hydrogen (H I) in the nearest interacting group of galaxies (that dominated by M81), obtained by combining 12 separate fields observed with the Very Large Array. The H I that surrounds M81, M82 and NGC3077 (the most prominent galaxies in the group) is dominated by filamentary structures, clearly demonstrating the violent disruption of this system by tidal interactions. These observations should have detected all H I complexes more massive than 10(6) solar masses, meaning that our map contains all structures that might evolve into new dwarf galaxies.

Astronomical Phenomena↗
PubMed1993

Selective perhydroxylation of squalene: taming the arithmetic demon.

Osmium-catalyzed asymmetric dihydroxylation, which produces 1,2-diols of high enantiopurity from prochiral olefins, is an example of the synthetic catalysts that have been developed that rival enzymes in their efficiency and high enantioselectivity. Although the asymmetric dihydroxylation catalyst lacks an enzyme's ability to effectively distinguish among the subtly different olefinic sites in a polyolefin such as squalene, this very inability permits it to bring about the "exhaustive" polyhydroxylation of squalene to give a dodecahydroxy derivative. Twelve chemical and stereochemical events proceed in tandem with a remarkable average yield of 98 percent per step, giving 1 out of the 36 possible stereoisomers in (0.98)12 = 78.9 percent overall yield.

Hydroxylation↗
PubMed1993

Prenatal detection of neuroblastoma: a ten-year experience from the Dana-Farber Cancer Institute and Children's Hospital.

OBJECTIVES: To assess the relative frequency of, the clinical and pathological correlates in, and the prognosis of the subset of infants with neuroblastoma who were identified initially by prenatal ultrasonography. DESIGN: Retrospective review of all patients with neuroblastoma evaluated between 1982 and 1992. SETTING: Large, urban, tertiary care children's hospital in Boston, Massachusetts. PATIENTS: Eleven infants with neuroblastoma initially detected with prenatal sonograms were identified. RESULTS: Nine patients had adrenal tumors; two had thoracic paraspinal tumors. Typical diagnostic evidence for neuroblastoma including a palpable abdominal mass and elevations in urinary catecholamines were not commonly seen postnatally. These patients had multiple favorable prognostic indicators including low stage of disease (10/11), favorable biological markers including cellular DNA content (5/5) and N-myc oncogene copy number (5/5), and histopathology suggestive for neuroblastoma in situ (7/11). All patients were treated by surgical resection. One patient exhibited progression of disease postoperatively, but demonstrated a complete clinical response to multiagent chemotherapy. Overall survival in our population was excellent with no deaths seen at a mean follow-up of 37 months (range 3 to 120 months). CONCLUSIONS: Patients with neuroblastoma identified by prenatal ultrasonography generally, although not exclusively, follow a clinically favorable course in which surgical resection is curative. Chemotherapy is not indicated unless substantial progression of disease occurs.

Adrenal Gland Neoplasms↗
PubMed1992

Characterization of the defect in a variant of HL-60 promyelocytic leukemia cells with reduced transferrin receptor expression.

The mechanism by which a clone of HL-60 human promyelocytic leukemia cells designated Tf-Gel-1 expresses reduced levels of the transferrin receptor (TfR) was investigated. Tf-Gel-1 was developed by continuous exposure of HL-60 cells to human iron-saturated transferrin covalently linked to the plant toxin gelonin (Tf-Gel); this variant was five- to sixfold more resistant to Tf-Gel than parental HL-60 cells. The amount of cell surface, as well as of solubilized, TfR and the cycling pools of TfR in Tf-Gel-1 cells, as measured by the binding of [125I]Tf, were all decreased to 20-30% of the levels present in parental cells. The growth of Tf-Gel-1 cells was independent of exogenous Fe3+ and was comparable to that of parental HL-60 cells. Despite the lower levels of TfRs, the Tf-Gel-1 clone retained the capacity to alter receptor expression, depending upon the phase of growth and the intracellular iron concentration, and to down-regulate TfRs in response to inducers of differentiation. Southern hybridization of cellular DNA with TfR cDNA did not reveal differences between parental and Tf-Gel-1 cells in the level and arrangement of the TfR gene. Basal and inducible (repressible) levels of TfR mRNA from Tf-Gel-1 cells, as measured by northern hybridization of cellular RNA with TfR cDNA, were comparable to those of parental cells. Metabolic labeling of cells with [35S]methionine, followed by immunoprecipitation of TfRs, demonstrated that the amount of radioactivity incorporated into TfRs in Tf-Gel-1 cells was reduced to a degree that approximated the decrease in [125I]Tf binding. Cell surface TfRs prepared from exponentially growing parental cells labeled with 125I by the solid-phase lactoperoxidase-glucose oxidase method existed as a doublet, with one form being phosphorylated and the other not phosphorylated. In contrast, Tf-Gel-1 cells not only contained diminished amounts of TfRs but also contained only the phosphorylated form of TfRs in the surface membrane. The decrease in the surface membrane concentration of the TfR in Tf-Gel-1 cells was specific for this glycoprotein, since the levels of other cell surface antigens, such as CD13, CD15 and CD45, were normal in Tf-Gel-1 cells. A reduction in the incorporation of [3H]mannose into the acid-insoluble fraction of cells and an increase in sensitivity to ricin suggested that Tf-Gel-1 cells possessed an aberration in carbohydrate metabolism.

Antigens, Surface↗
PubMed1991

Non-sequence-specific inhibition of transferrin receptor expression in HL-60 leukemia cells by phosphorothioate oligodeoxynucleotides.

A series of phosphodiester and phosphorothioate antisense oligodeoxynucleotides were synthesized against the human transferrin receptor (TfR). The phosphorothioate analogs exhibited marked biologic efficacy in culture, as assessed by inhibition of surface TfR content and HL-60 cell growth, whereas their unmodified phosphodiester counterparts were ineffective. Phosphorothioate oligodeoxynucleotides were more resistant to hydrolysis by serum and cellular nucleases and were more readily taken up by cells than phosphodiesters, thus providing a partial explanation for the differences in biologic activity. A length effect was observed, with antisense 30-mers exhibiting greater TfR inhibitory activity than 17-mers. The degree of receptor inhibition observed, however, was not sequence dependent, suggesting that the phosphorothioate oligodeoxynucleotides may have pleiotropic activities in eukaryotic cells in addition to inhibiting gene expression by classic antisense complementary binding to mRNA.

Base Sequence↗