Changes in the N- and C-terminal sequences of the murine R7 Gag-tMos protein affect brain lesion induction

Our preliminary studies suggested that the novel gag-truncated mos (tmos) open reading frame (ORF) of R7, a spontaneous deletion mutant of Moloney murine sarcoma virus 124 (MoMuSV124), may be responsible for R7's unique ability to induce brain lesions in all R7-injected mice. However, when we replaced the gag-tmos ORF with either the MoMuSV124 or the homologous myeloproliferative sarcoma virus env-mos gene, we found that both recombinant viruses also induced brain lesions in all injected mice. Although these studies suggested that the critical determinants for brain lesion induction may reside in the tmos sequence common to all three viruses, they did not demonstrate if the N-terminus of Mos was dispensable for this activity. By inserting the FLAG sequence at the 3' end of the R7 gag-tmos ORF, we demonstrated that R7 does synthesize a Gag-tMos fusion protein. Using R7 gag deletion mutants with and without the FLAG sequence, we further demonstrated that (i) deletion of the entire gag sequence abolished R7's transforming activity; (ii) the ability of the virus to transform cultured NIH/3T3 cells was significantly reduced only when most of gag was deleted; (iii) the ability of the virus to induce brain lesions was inversely proportional to the extent of its gag deletions; and (iv) the insertion of FLAG at the Mos C-terminus did not reduce the in vitro transforming activity of the FLAG-tagged viruses but did reduce their ability to induce brain lesions. Thus, we have demonstrated that altering the N- or C-terminus of the R7 Gag-tMos fusion protein can affect disease manifestation.     

Spontaneously relapsing clonal, mucosal cytotoxic T-cell lymphoproliferative disorder: case report and review of the literature

Primary T-cell lymphoma of the gastrointestinal tract is a rare and usually aggressive disorder that may be associated with celiac disease. The authors describe a unique case of a clonal proliferation of CD8+ T cells involving the oral mucosa, ileum, and colon of a 35-year-old man that has regressed spontaneously and recurred numerous times over a 9-year period without treatment. The patient's symptoms were limited to occasional rectal bleeding and recurring painful oral ulcers. Within the intestine, these collections of small T cells induced minimal architectural distortions and did not show extensive epitheliotrophism. Polymerase chain reaction and sequencing analyses revealed that the identical T-cell clone has been present for more than 9 years and in different mucosal locations in this patient. This may represent a unique T-cell lymphoproliferative process akin to a mucosal counterpart of lymphomatoid papulosis of the skin.     

香港头颈外科的发展现状

头颈外科包括了头颈部肿瘤及相关疾病的诊断和治疗。香港头颈外科的起源可以追述到本世纪60年代中期。当时的香港大学玛丽医院外科学系主任王源美教授是开创这一领域的先驱。香港最初只有普外科医生涉及到这一区域肿瘤的治疗，经过多年来其它专科的发展，目前香港头颈部的疾病已经可以由三个外科次级专科处理，即耳鼻喉科、整形重建科和普外科。20年来，在外科、放射科及化疗科的共同努力下，头颈部肿瘤在诊断及治疗方面获得的迅速的发展，这就使病人的预后得到了很大程度的改善。     

Second cancers after medulloblastoma: population-based results from the United States and Sweden

Medulloblastoma, one of the most common central nervous system(CNS)tumors in children, requires aggressive multimodality therapy including surgery, radiation therapy, and occasionally chemotherapy. Given its intensive treatment regimen and improved survival during the past 20 years, it is likely that a cohort of survivors will result who may incur consequences of therapy, including a second cancer. We used population-based data from the United States and Sweden to estimate risks of second neo plasms in patients with histologically confirmed medulloblastoma (n = 1,262).Overall, there was a 5.4-fold excess of second neoplasms (95 percent confidence interval = 3.3-8.4) based on 20 observed and 3.7 expected cancers. The second cancers occurred eight to 432 months after initial diagnosis(median, 73 months) with significantly elevated ratios for all intervals examined except for less than one year after initial diagnosis. Significantly elevated risks were seen for cancers of the salivary glands, cervix uteri, brain and CNS, thyroid gland, and acute lymphoblastic leukemia. Of the 15second cancers with treatment data, seven occurred in the radiation field or within areas of scatter while two others may have been radiation-related. Although based on small numbers of second cancers, the results suggest that as survival increases, some patients with medulloblastoma will have an increased risk of a second cancer, particularly a radiation-related cancer. Thus, as survival improves, late-occurring consequences of diagnosis and treatment will need to be carefully assessed. Identification of patients hypersensitive to radiation therapy, such as those with Gorlin Syndrome, should also be attempted in order to reduce the sequelae from intensive radiation exposure. This revised version was published online in July 2006 with corrections to the Cover Date.     

Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft

The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-daily 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in three different schedules: (1) i.p. as a single bolus (SB) or (2) i.p. as a daily bolus at 30 min before the first daily radiation fraction or (3) s.c. as a continuous infusion through a mini-osmotic pump over 13 days, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as the difference between the delay in regrowth to 200% of the initial tumour size in treated versus control mice. SB cisplatin plus radiation showed only an additive effect on TGD, whereas daily-bolus and continuous-infusion cisplatin demonstrated a greater than additive effect when combined with accelerated fractionated radiation in this human tumour model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation. Received: 15 December 1996 / Accepted: 25 March 1997     

Population dose due to natural radiation in Hong Kong

In densely populated cities such as Hong Kong where people live and work in high-rise buildings that are all built with concrete, the indoor gamma dose rate and indoor radon concentration are not wide ranging. Indoor gamma dose rates (including cosmic rays) follow a normal distribution with an arithmetic mean of 0.22 +/- 0.04 microGy h(-1), whereas indoor radon concentrations follow a log-normal distribution with geometric means of 48 +/- 2 Bq m(-3) and 90 +/- 2 Bq m(-3) for the two main categories of buildings: residential and non-residential. Since different occupations result in different occupancy in different categories of buildings, the annual total dose [indoor and outdoor radon effective dose + indoor and outdoor gamma absorbed dose (including cosmic ray)] to the population in Hong Kong was estimated based on the number of people for each occupation; the occupancy of each occupation; indoor radon concentration distribution and indoor gamma dose rate distribution for each category of buildings; outdoor radon concentration and gamma dose rate; and indoor and outdoor cosmic ray dose rates. The result shows that the annual doses for every occupation follow a log-normal distribution. This is expected since the total dose is dominated by radon effective dose, which has a log-normal distribution. The annual dose to the population of Hong Kong is characterized by a log-normal distribution with a geometric mean of 2.4 mSv and a geometric standard deviation of 1.3 mSv.     

Drop‐offs in the isoniazid preventive therapy cascade among children living with HIV in western Kenya, 2015–2019

IntroductionIsoniazid preventive therapy (IPT) can reduce the risk of tuberculosis (TB) in children living with HIV (CLHIV), but data on the outcomes of the IPT cascade in CLHIV are limited.MethodsWe evaluated the IPT cascade among CLHIV aged <15 years and newly enrolled in HIV care in eight HIV clinics in western Kenya. Medical record data were abstracted from September 2015 through July 2019. We assessed the proportion of CLHIV completing TB symptom screening, IPT eligibility assessment, IPT initiation and completion. TB incidence rate was calculated stratified by IPT initiation and completion status. Risk factors for IPT non‐initiation and non‐completion were assessed using Poisson regression with generalized linear models.ResultsOverall, 856 CLHIV were newly enrolled in HIV care, of whom 98% ([95% CI 97–99]; n = 841) underwent screening for TB symptoms and IPT eligibility. Of these, 13 (2%; 95% CI 1–3) were ineligible due to active TB and 828 (98%; 95% CI 97–99) were eligible. Five hundred and fifty‐nine (68%; 95% CI 64–71) of eligible CLHIV initiated IPT; median time to IPT initiation was 3.6 months (interquartile range [IQR] 0.5–10.2). Overall, 434 (78%; 95% CI 74–81) IPT initiators completed. Attending high‐volume HIV clinics (aRR = 2.82; 95% CI 1.20–6.62) was independently associated with IPT non‐initiation. IPT non‐initiation had a trend of being higher among those enrolled in the period 2017–2019 versus 2015–2016 (aRR = 1.91; 0.98–3.73) and those who were HIV virally non‐suppressed (aRR = 1.90; 95% CI 0.98–3.71). Being enrolled in 2017–2019 versus 2015–2016 (aRR = 1.40; 1.01–1.96) was independently associated with IPT non‐completion. By 24 months after IPT screening, TB incidence was four‐fold higher among eligible CLHIV who never initiated (8.1 per 1000 person years [PY]) compared to CLHIV who completed IPT (2.1 per 1000 PY; rate ratio [RR] = 3.85; 95% CI 1.08–17.15), with a similar trend among CLHIV who initiated but did not complete IPT (8.2/1000 PY; RR = 4.39; 95% CI 0.82–23.56).ConclusionsDespite high screening for eligibility, timely IPT initiation and completion were suboptimal among eligible CLHIV in this programmatic cohort. Targeted programmatic interventions are needed to address these drop‐offs from the IPT cascade by ensuring timely IPT initiation after ruling out active TB and enhancing completion of the 6‐month course to reduce TB in CLHIV.     

Differing concentrations of human chorionic gonadotropin and prolactin in the cyst fluid of hydatidiform mole and in amniotic fluid

The concentrations of human chorionic gonadotropin and prolactin in the cyst fluid of molar tissue were compared with that of normal amniotic fluid. Molar fluid was aspirated from the vesicles of molar tissue in eight women (duration of amenorrhea 14.1 +/- 1 week, mean +/- SEM). Amniotic fluid was obtained at amniocentesis in 24 women (mean duration of amenorrhea 15.9 +/- 0.2 week). Hormones were measured by specific radioimmunoassay. The concentrations (mean +/- SEM) of human chorionic gonadotropin in molar fluid and amniotic fluid were 581,829 +/- 112,581 and 3187 +/- 505 mlU/ml (p less than 0.001), respectively. For prolactin the levels in molar fluid and amniotic fluid were 44 +/- 24 and 1962 +/- 313 ng/ml (p less than 0.001), respectively. These data demonstrate that molar fluid contains 182-fold higher levels of human chorionic gonadotropin and 45-fold lower levels of prolactin than amniotic fluid obtained from normal pregnant women with a similar duration of amenorrhea. In addition to altered endocrine function of the trophoblast, there may be altered prolactin secretion from the decidua in molar pregnancy as compared with normal pregnancy. Further research is required to evaluate prolactin production from decidua of molar pregnancy.     

Ocular fluorophotometry in the normal- and diabetic monkey

Normal- and diabetic rhesus monkeys without retinopathy demonstrable by ophthalmoscopy or fluorescein angiography were examined with ocular fluorophotometry to detect alterations in their blood-ocular barriers. All vitreous fluorophotometry values were corrected for fluorescence attributable to background levels and then normalized to a blood fluorescein level of 10 micrograms ml-1. Reproducibility studies demonstrated an average coefficient of variation of 0.17 for all animals combined. Insulin-dependent monkeys, both pancreatectomized and streptozotocin-treated, demonstrated significantly higher posterior vitreous fluorescence levels than either control animals or monkeys treated with streptozotocin that were not insulin-dependent. These results cannot be attributed to differences in fluorescein binding or to vitreous abnormalities. However, 14 out of 24 (58%) of the insulin-dependent animals exhibited posterior vitreous fluorescence values within two standard deviations of the control mean. No correlation was apparent between the vitreous values and age or duration of treatment. No difference in anterior chamber concentrations was found between groups after correction. Our results indicate that alterations in blood-retinal barrier can occur in insulin-dependent diabetic monkeys before development of retinopathy.