Imaging quiz case 2. First branchial cleft cyst (FBCC).
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Branchioma↗
Biomedical subjects
S Ho
Publications and source records attributed to S Ho.
The nature of the principal type 1 interferon-producing cells in human blood.
Interferons (IFNs) are the most important cytokines in antiviral immune responses. "Natural IFN-producing cells" (IPCs) in human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated and further characterized because of their rarity, rapid apoptosis, and lack of lineage markers. Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge. pDC2s are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.
CD40 Ligand↗
Activity patterns and synaptic organization of ventrally located interneurons in the embryonic chick spinal cord.
To investigate the origin of spontaneous activity in developing spinal networks, we examined the activity patterns and synaptic organization of ventrally located lumbosacral interneurons, including those whose axons project into the ventrolateral funiculus (VLF), in embryonic day 9 (E9)-E12 chick embryos. During spontaneous episodes, rhythmic synaptic potentials were recorded from the VLF and from spinal interneurons that were synchronized, cycle by cycle, with rhythmic ventral root potentials. At the beginning of an episode, ventral root potentials started before the VLF discharge and the firing of individual interneurons. However, pharmacological blockade of recurrent motoneuron collaterals did not prevent or substantially delay interneuron recruitment during spontaneous episodes. The synaptic connections of interneurons were examined by stimulating the VLF and recording the potentials evoked in the ventral roots, in the VLF, or in individual interneurons. Low-intensity stimulation of the VLF evoked a short-latency depolarizing potential in the ventral roots, or in interneurons, that was probably mediated mono- or disynaptically. At higher intensities, long-latency responses were recruited in a highly nonlinear manner, eventually culminating in the activation of an episode. VLF-evoked potentials were reversibly blocked by extracellular Co2+, indicating that they were mediated by chemical synaptic transmission. Collectively, these findings indicate that ventral interneurons are rhythmically active, project to motoneurons, and are likely to be interconnected by recurrent excitatory synaptic connections. This pattern of organization may explain the synchronous activation of spinal neurons and the regenerative activation of spinal networks when provided with a suprathreshold stimulus.
Activity Cycles↗
Spontaneous network activity transiently depresses synaptic transmission in the embryonic chick spinal cord.
We examined the effects of spontaneous or evoked episodes of rhythmic activity on synaptic transmission in several spinal pathways of embryonic day 9-12 chick embryos. We compared the amplitude of synaptic potentials evoked by stimulation of the ventrolateral funiculus (VLF), the dorsal or ventral roots, before and after episodes of activity. With the exception of the short-latency responses evoked by dorsal root stimulation, the potentials were briefly potentiated and then reduced for several minutes after an episode of rhythmic activity. Their amplitude progressively recovered in the interval between successive episodes. The lack of post-episode depression in the short-latency component of the dorsal root evoked responses is probably attributable to the absence of firing in cut muscle afferents during an episode of activity. The post-episode depression of VLF-evoked potentials was mimicked by prolonged stimulation of the VLF, subthreshold for an episode of activity. By contrast, antidromically induced motoneuron firing and the accompanying calcium entry did not depress VLF-evoked potentials recorded from the stimulated ventral root. In addition, post-episode depression of VLF-evoked synaptic currents was observed in voltage-clamped spinal neurons. Collectively, these findings suggest that somatic postsynaptic activity and calcium entry are not required for the depression. We propose instead that the mechanism may involve a form of long-lasting activity-induced synaptic depression, possibly a combination of transmitter depletion and ligand-induced changes in the postsynaptic current accompanying transmitter release. This activity-dependent depression appears to be an important mechanism underlying the occurrence of spontaneous activity in developing spinal networks.
Animals↗
Sam Ho, MD: idealist, innovator, entrepreneur. Interview by Fitzhugh Mullan.
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Administrative Personnel↗
Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults.
OBJECTIVE: To study the acute and steady-state cognitive effects of three new antiepileptic drugs (AEDs): gabapentin, lamotrigine, and topiramate. BACKGROUND: Several newer antiepileptic medications approved recently by the Food and Drug Administration are gaining attention as efficacious alternatives to established AEDs. Greater tolerability with fewer side effects are reported in some. However, the potential cognitive effects of these newer AEDs have received limited attention. METHODS: Healthy young adults randomized to either of the three drugs were administered tests of attention, psychomotor speed, language, memory, and mood at baseline (predrug), acute single-dose period, and after 2 and 4 weeks on the drug. RESULTS: Compared with baseline, the topiramate group had selective, statistically significant declines on measures of attention and word fluency at acute doses, whereas the other two AED groups had no performance changes. At the 2- and 4-week test periods, only the topiramate subjects continued to display neurocognitive effects from drug administration. CONCLUSIONS: Results demonstrate potential acute and steady-state adverse cognitive effects for topiramate, whereas minimal effects were displayed for either gabapentin or lamotrigine in young healthy adults.
Acetates↗
Phase II studies with DaunoXome in patients with nonresectable hepatocellular carcinoma: clinical and pharmacokinetic outcomes.
A total of 14 Chinese patients with inoperable hepatocellular carcinoma received a liposomal formulation of daunorubicin (DaunoXome) at a dose equivalent to 100 mg/m2 of the free drug every 3 weeks. Altogether, 12 patients were assessable for response; 2 patients had stable disease for 8 weeks, but all eventually developed progressive disease and there was no responder. The drug was well tolerated, with no evidence of cardiac toxicity being observed. Deterioration of liver-function tests was attributed to progressive tumors in the terminal stage of the disease. Pharmacokinetics studies revealed a biexponential decay for daunorubicin in association with mean initial and terminal half-lives of 1.8 and 7.4 h, respectively, and a mean total clearance of 15.0+/-5.5 ml/min. The AUC ratio between the metabolite daunorubicinol and daunorubicin was 0.07. These data differ markedly from the pharmacokinetics of the free drug.
Adult↗
Mucin gene expression in the rat middle ear: an improved method for RNA harvest.
Mucins are heavily glycosylated proteins characterized by high molecular weight and heterogeneous structure. Mucin genes are expressed in a tissue- or epithelium-specific manner. Although mucins are known to be important structural components of the mucociliary transport system that protects epithelium against invading microorganisms, very little is known about mucin gene expression unique to the middle ear. This study demonstrated that middle ear messenger RNA specifically hybridized with rat MUC2 and human MUC2 (SMUC-41) complementary DNA probes. MUC3 and MUC5AC mucin genes, dominantly expressed in rodent intestine and trachea, were not detected in the rat middle ears in this study. The middle ear MUC2 messenger RNA harvested by lavage was characterized by a single transcript--unlike its counterpart in intestine and airways, which is characterized by polydispersity--suggestive of a better method for RNA analysis. It was concluded that rat middle ears possess a MUC2 mucin gene or homologue of human MUC2 (SMUC-41).
Animals↗
Combating hepatocellular carcinoma with an integrated approach.
This short review summarizes an integrated approach to new methods of managing hepatocellular carcinoma (HCC) developed at our centre. HCC-specific isoforms of alpha-fetoprotein were detected by isoelectric focusing and their value in the differential diagnosis of early HCC on a background of chronic liver disease has been shown. Selective internal radiation therapy using yttrium-90 (90 Y) microspheres has been shown to be an effective treatment for inoperable HCC in a phase I and II study. A partition model for estimating the radiation doses from the 90 Y microspheres to the tumour and the non-tumorous liver during the therapy was then formulated, verified by correlating with intraoperative dosimetry, and evaluated in clinical settings. This permits 90 Y microspheres to be administered safely without the need of an open surgery and a randomized therapeutic controlled trial is in progress. Another randomized controlled trial using iodine-131 Lipiodol as a post-operative adjuvant therapy, aiming at reducing the recurrence rate is also on-going. HCC may be more effectively combated with a better understanding of its pathogenesis from chronic liver disease.
Carcinoma, Hepatocellular↗
Internal radiation therapy for patients with primary or metastatic hepatic cancer: a review.
BACKGROUND: The limited efficacy of current approaches to the treatment of patients with hepatic cancer, including external beam radiation therapy and cytotoxic chemotherapy, has reawakened interest in the use of internal radiation therapy. METHODS: The authors reviewed series of patients with liver metastases or hepatocellular carcinoma (HCC) treated with 1) interstitial irradiation and direct intratumoral injection of 90Y microspheres, 2) intraarterial infusion of (131)I-Lipiodol, 3) intraarterial infusion of 90Y microspheres, or 4) parenteral administration of radiolabeled monoclonal antibodies. RESULTS: High dose rate interstitial irradiation with afterloading of (192)Ir resulted in local control of hepatic metastases for a median of 8 months and complete tumor eradication in 2 patients. Direct intratumoral injection of 90Y microspheres reduced the size of 90.6% of tumors and completely destroyed them in 8 patients. Treatment with arterial (131)I-Lipiodol resulted in a 17-92% response rate as well as a case of complete remission of unresectable HCC. It was found to be most effective against small tumors. No response was observed with liver metastases from colorectal carcinoma. Partial response was commonly achieved when patients with unresectable liver metastases or HCC were treated with intraarterial 9OY microspheres. Among four patients whose HCC became resectable following treatment with 90Y microspheres, two cases of complete remission were documented. In a prospective randomized trial, (131)I-antiferritin combined with chemotherapy was no more effective than chemotherapy alone. CONCLUSIONS: The different approaches to internal radiation therapy that are reviewed in this article represent several ways in which radiation can be selectively targeted to hepatic tumors without undue radiation to the nontumorous liver. However, the efficacy of each of these therapies still needs to be evaluated in randomized controlled trials.
Brachytherapy↗
Human alpha1,3/4-fucosyltransferases. I. Identification of amino acids involved in acceptor substrate binding by site-directed mutagenesis.
In a previous study (Xu, Z., Vo, L., and Macher, B. A. (1996) J. Biol. Chem. 271, 8818-8823), a domain swapping approach demonstrated that a region of amino acids found in human alpha1, 3/4-fucosyltransferase III (FucT III) conferred a significant increase in alpha1,4-FucT acceptor substrate specificity into alpha1, 3-fucosyltransferase V (FucT V), which, under the same assay conditions, has extremely low alpha1,4-FucT acceptor substrate specificity. In the current study, site-directed mutagenesis was utilized to identify which of the eight amino acids, associated with alpha1,4-FucT acceptor substrate specificity, is/are responsible for conferring this new property. The results demonstrate that increased alpha1,4-FucT activity with both disaccharide and glycolipid acceptors can be conferred on FucT V by modifying as few as two (Asn86 to His and Thr87 to Ile) of the eight amino acids originally swapped from FucT III into the FucT V sequence. Neither single amino acid mutant had increased alpha1,4-FucT activity relative to that of FucT V. Kinetic analyses of FucT V mutants demonstrated a reduced Km for Galbeta1,3GlcNAc (type 1) acceptor substrates compared with native FucT V. However, this was about 20-fold higher than that found for native FucT III, suggesting that other amino acids in FucT III must contribute to its overall binding site for type 1 substrates. These results demonstrate that amino acid residues near the amino terminus of the catalytic domain of FucT III contribute to its acceptor substrate specificity.
Amino Acid Sequence↗
Selective internal radiation therapy for nonresectable hepatocellular carcinoma with intraarterial infusion of 90yttrium microspheres.
PURPOSE: To evaluate the efficacy of intraarterial 90yttrium (90Y) microspheres in nonresectable hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Patients with nonresectable HCC, but without extrahepatic disease, who also had lung shunting < 15% and tumor-to-normal ratio > or =2, as determined by simulation using (99m)technetium macroaggregated albumin, were entered into the study. The radiation dose delivered to the lungs, tumor, and normal liver was estimated by a partition model. 90Y microspheres were infused into the hepatic artery at the time of hepatic angiography or through an implanted arterial portacatheter under fluoroscopy. Repeated treatments were given for residual or recurrent tumor. Response to treatment was monitored by serum alpha-fetoprotein or ferritin levels, together with serial computed tomography. RESULTS: Seventy-one patients, including 20 patients with postoperative recurrence, were initially treated with an activity of 0.8 to 5.0 Giga-Becquerel (GBq) (21.6-135.1 mCi) (median 3.0 GBq or 81.1 mCi) of 90Y microspheres. There was a 50% reduction in tumor volume in 19 (26.7%) patients after the first treatment. However, the overall objective response in terms of changes in alpha-fetoprotein levels was 89% [partial response (PR) 67%, complete response (CR) 22%] among the 46 patients with raised pretreatment levels. The serum ferritin level in the other 25 patients dropped by 34 to 99% after treatment. Treatment was repeated in 15 patients. The maximum number of treatments was 5 and the maximum total activity was 13.0 GBq (351.4 mCi), given in 3 treatments. The estimated radiation doses to the nontumorous liver ranged from 25 to 136 Gy (median 52 Gy) in the first treatment and the highest total radiation dose was estimated to be 324 Gy. For the tumors, the estimated radiation doses ranged from 83 to 748 Gy (median 225 Gy) in the initial treatment and the highest cumulative dose reached was 1580 Gy. The residual tumors were resected in 4 patients. Two of these had complete histological remission, but only occasional viable tumor cells were found in the necrotic centers of the tumors resected from the other 2 patients. The median survival of the 71 patients was 9.4 months (range 1.8 to 46.4 months). Treatment was well tolerated and there was no bone-marrow toxicity, or clinical evidence of radiation hepatitis or pneumonitis. CONCLUSIONS: Selective internal radiation therapy using 90Y microspheres is effective for selected cases of nonresectable HCC and is well tolerated. The objective response rate in terms of drop in tumor marker levels is higher than that based on reduction in tumor volume shown by computed tomography. The nontumorous liver appears more tolerant to internal radiation than external beam radiation. Selective internal radiation treatment may convert nonresectable tumors to resectable ones.
Adult↗
Cholecystectomy in cardiothoracic organ transplant recipients.
OBJECTIVES: To assess the risks associated with cholelithiasis and cholecystectomy in cardiothoracic organ transplant recipients at this hospital and to identify any differences with potential causal significance between the group with known gallstones and the transplant recipient group as a whole. DESIGN: Medical records survey. SETTING: Tertiary care university hospital. PATIENTS: Six hundred forty-five patients had cardiothoracic organ transplantation at this hospital between February 1, 1984, and May 31, 1996. Gallstones were detected in 37 (5.7%) of these patients and 32 patients underwent cholecystectomy, of which 29 operations were performed primarily for symptomatic gallstone disease. All cholecystectomies were performed after transplantation. MAIN OUTCOME MEASURES: Mortality, morbidity, postoperative biliary disease. RESULTS: Patients with gallstones were significantly older than the transplant patient group as a whole (Student t test, P=.001); they were more likely to be female (chi2 test, P=.05); and they had a higher body mass index (t test, P=.001). There were no significant differences in the maximum serum bilirubin level during the transplantation admission, incidence of diabetes mellitus, cholestyramine use, or cyclosporine dosage during the first 12 months after transplantation. Cholecystectomy was performed after a median 5-month symptomatic period, mostly by the minilaparotomy method. Forty-five percent of cholecystectomies were urgent or semi-urgent. One patient died of lung infection on the second postoperative day. The median postoperative stay was 3 days. At a median 33 months' follow-up, 4 patients have had further biliary problems (2 patients with common bile duct stones, 1 patient with intrahepatic stones, and 1 patient with biliary dyskinesia). Four other patients with asymptomatic gallstones who did not receive cholecystectomy have remained asymptomatic for between 15 and 67 months. CONCLUSIONS: Cholecystectomy by the minilaparotomy or laparoscopic methods, with routine operative cholangiography, is the preferred treatment for symptomatic gallstones in cardiothoracic organ transplant recipients. Although the optimum management of asymptomatic gallstones in these patients remains unclear, our favorable experience with a policy of reserving cholecystectomy for symptomatic cases seems noteworthy.
Adolescent↗
New development of laparoscopic ultrasound and laparoscopic pelvic lymphadenectomy in the management of patients with cervical carcinoma.
OBJECTIVES: The objectives of this study were to evaluate the use of laparoscopic ultrasonography (USG) in combination with laparoscopic pelvic lymphadenectomy in the management of patients with cervical carcinoma. METHODS: A technique for detecting pelvic and para-aortic lymph node metastases through laparoscopic USG was developed. Laparoscopic USG was done prior to pelvic lymphadenectomy performed either laparoscopically or by laparotomy. Laparoscopic USG findings were compared with pathologic findings. RESULTS: The sensitivity and specificity of laparoscopic USG in detecting pelvic lymph node metastases were 91 and 100%, respectively. Metastatic pelvic lymph nodes could be completely removed through laparoscopes in 7 of 11 patients, with no complications. CONCLUSION: Laparoscopic USG is highly sensitive in detecting metastatic pelvic lymph nodes. Detection and removal of metastatic pelvic lymph nodes laparoscopically allow quick recovery from the operation and early commencement of radiotherapy.
Adult↗
Apoptosis of JHMV-specific CTL in the CNS in the absence of CD4+ T cells.
The role of CD4+ T cells in altering the activity of cytotoxic T lymphocytes (CTL) during infection of the central nervous system (CNS) by the neuroptropic JHMV strain of mouse hepatitis virus was examined. Adoptive transfer of in vitro activated CTL into CD4-depleted and control recipients showed that CTL were not effective in reducing JHMV replication within the CNS. The distribution of CD4+ and CD8+ T cells within the CNS during JHMV infection showed that the CD4+ T cells remained in perivascular and subarachnoid spaces and few entered the parenchyma. By contrast approximately half of the CD8+ T cells entered the parenchyma. In CD4-depleted mice the trafficking of CD8+ T cells was not inhibited; however, the majority of the cells were found to be apoptotic. These data suggested that CD4+ T cells were not required for CTL induction but were required for the maintenance of CTL viability. The limited role of CD4+ T cells in CTL induction was confirmed by comparison of CTL activity from CD4-depleted and control mice.
Adoptive Transfer↗
The angiographic diagnosis of colonic carcinoma.
Carcinoma of the colon is a common cause of chronic iron deficiency anaemia in elderly patients and is conventionally diagnosed by either barium enema or colonoscopy. Occasionally these studies are inconclusive and individuals may proceed to further imaging, including angiography. Between December 1991 and October 1996, 337 patients were referred for visceral angiography to determine the cause of chronic gastrointestinal bleeding. In seven of these individuals (two males and five females with an age range of 65-74 years), all of whom had been investigated by barium enema and colonoscopy, both reported as showing no cause for bleeding, an arteriographic diagnosis of colonic carcinoma was made. Four of these demonstrated patchy areas of increased vascularity whilst three were predominantly hypovascular. Early venous drainage was seen in five. Marked irregularity and truncation of vasa rectae was present in six; more subtle irregularity was visible in one. The mural veins were irregular with or without truncation in five of the six patients in whom they were visualized. The marginal artery was angiographically involved in only two cases and in one of these the tumour was irresectable. It is important to recognize that a previous 'normal' colonoscopy and barium enema does not exclude a colonic neoplasm, even if advanced, and that this diagnosis may be made angiographically. Confusion with other pathologies, such as angiodysplasia, should be prevented by close scrutiny of vasa rectae at the site of arteriographic abnormality, which will usually demonstrate vascular irregularity and truncation highly suggestive of malignancy.
Aged↗
Staging and IgA VCA titre in patients with nasopharyngeal carcinoma: changes over a 12-year period.
The distributions of 2093 patients with nasopharyngeal carcinoma (NPC), by stage, over a 12-year-period did not show any evidence of a shift towards early stages despite growing awareness of this prevalent malignancy. The IgA VCA titre was determined for 1880 of these patients. The median titre increased from 40 in stage I to 80 in stages II, III, and IV, before rising to 160 in stage V. The percentage of patients with a titre > or = 320 increased steadily with advancing stages. Within the same disease stage, the percentage of patients having a particular titre value and the median titre varied considerably from year to year. Better education of the general population and a better serological marker for screening are needed for the early detection of NPC.
Antibodies, Neoplasm↗
Detection of alphafetoprotein-expressing cells in the blood of patients with hepatoma and hepatitis.
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Carcinoma, Hepatocellular↗