Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit.

In eukaryotic cells, nuclear export of nascent ribosomal subunits through the nuclear pore complex depends on the small GTPase Ran. However, neither the nuclear export signals (NESs) for the ribosomal subunits nor the receptor proteins, which recognize the NESs and mediate export of the subunits, have been identified. We showed previously that Nmd3p is an essential protein from yeast that is required for a late step in biogenesis of the large (60S) ribosomal subunit. Here, we show that Nmd3p shuttles and that deletion of the NES from Nmd3p leads to nuclear accumulation of the mutant protein, inhibition of the 60S subunit biogenesis, and inhibition of the nuclear export of 60S subunits. Moreover, the 60S subunits that accumulate in the nucleus can be coimmunoprecipitated with the NES-deficient Nmd3p. 60S subunit biogenesis and export of truncated Nmd3p were restored by the addition of an exogenous NES. To identify the export receptor for Nmd3p we show that Nmd3p shuttling and 60S export is blocked by the Crm1p-specific inhibitor leptomycin B. These results identify Crm1p as the receptor for Nmd3p export. Thus, export of the 60S subunit is mediated by the adapter protein Nmd3p in a Crm1p-dependent pathway.

NMD3 encodes an essential cytoplasmic protein required for stable 60S ribosomal subunits in Saccharomyces cerevisiae.

A mutation in NMD3 was found to be lethal in the absence of XRN1, which encodes the major cytoplasmic exoribonuclease responsible for mRNA turnover. Molecular genetic analysis of NMD3 revealed that it is an essential gene required for stable 60S ribosomal subunits. Cells bearing a temperature-sensitive allele of NMD3 had decreased levels of 60S subunits at the nonpermissive temperature which resulted in the formation of half-mer polysomes. Pulse-chase analysis of rRNA biogenesis indicated that 25S rRNA was made and processed with kinetics similar to wild-type kinetics. However, the mature RNA was rapidly degraded, with a half-life of 4 min. Nmd3p fractionated as a cytoplasmic protein and sedimented in the position of free 60S subunits in sucrose gradients. These results suggest that Nmd3p is a cytoplasmic factor required for a late cytoplasmic assembly step of the 60S subunit but is not a ribosomal protein. Putative orthologs of Nmd3p exist in Drosophila, in nematodes, and in archaebacteria but not in eubacteria. The Nmd3 protein sequence does not contain readily recognizable motifs of known function. However, these proteins all have an amino-terminal domain containing four repeats of Cx2C, reminiscent of zinc-binding proteins, implicated in nucleic acid binding or protein oligomerization.

Anaerobic membrane bioreactor for treatment of synthetic municipal wastewater at ambient temperature.

Non-woven fabric filter and poly-tetrafluoroethylene (PTFE) composite membrane were investigated to determine their applicability to treat low strength wastewater in an anaerobic membrane bioreactor (AMBR). Sludge cake resistance of the membrane was quantified using pure water flux of anaerobic sludge cake accumulated on the glass fiber filter of similar pore size. It is hypothesized that the formation of thin cake layer on the porous medium, e.g. non-woven and PTFE acts as a dynamic membrane. Thus, the capture of thin sludge cake inside the non-woven fabric matrix and accumulation on the PTFE membrane surface forms a membrane system equivalent to a commercial membrane system. The permeate quality was found to improve as the cake became more dense with filtration time. The PTFE composite membrane coated with thin PTFE film on the non-woven fabric filter enhanced the filtration performance by improving flux and minimizing the propensity of bio-fouling. The membrane flux was restored by back-flushing with permeate. The AMBR coupled with PTFE laminated membrane was operated continuously during the experiment at a cross flow velocity (CFV) of 0.1-0.2 m/sec and a transmembrane pressure (TMP) of 0.5-3 psi. Although about a month of acclimation was required to reach steady state, the effluent chemical oxygen demand (COD), volatile fatty acids (VFAs) as acetic acid, and suspended solids (SS) concentrations were below 30, 20 and 10 mg/L, respectively, during 90 days of operation with intermittent back washing. The lower operation TMP and CFV were subjected to less shear stress on the microbial community during continuous AMBR operation. In addition, thin sludge film accumulated on the membrane surface also acted as a biofilm bioreactor to remove additional COD in this study.

Cantonese-style salted fish as a cause of nasopharyngeal carcinoma: report of a case-control study in Hong Kong.

Two hundred fifty incident cases of nasopharyngeal carcinoma under age 35 years in Hong Kong Chinese and an equal number of age- and sex-matched friend controls were interviewed. Mothers of cases and controls were interviewed also, if available, to obtain information on childhood events concerning the study subjects. Consumption of Cantonese-style salted fish during all time periods was significantly associated with nasopharyngeal carcinoma; the association was especially strong during childhood. The relative risk for having Cantonese-style salted fish as one of the first solid foods during weaning was 7.5 (95% confidence limits, 3.9, 14.8), and the relative risk for consuming the food at least once a week compared to less than once a month at age 10 years was 37.7 (95% confidence limits, 14.1, 100.4). It is estimated that over 90% of young nasopharyngeal carcinoma cases in Hong Kong Chinese can be attributed to consumption of this food during childhood.

Early effects of cranial irradiation on hypothalamic-pituitary function.

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.

Adjunctive chemotherapy to radical radiation therapy in the treatment of advanced nasopharyngeal carcinoma.

Sixty-eight consecutive patients with previously untreated nasopharyngeal carcinoma (NPC) with advanced cervical lymph nodal metastases were studied retrospectively for the effectiveness of combining chemotherapy with radical radiation therapy (RT). In 1981 and 1982, 36 patients were treated with radical radiation therapy alone (arm 1). In 1983, 13 patients were given 2 courses of VBMF prior to RT (arm 2). In 1984, 19 patients were given radical RT sandwiched between 2 courses of PVBMF before and 2 after (arm 3). The three arms were comparable in patient characteristics with similar stages of the disease, sex, age distribution, and rates of completion of the prescribed treatments. There was no significant difference in actuarial or disease-free survival between arm 1 and 3 or arm 2 and 3, but arm 1 compared favorably with arm 2 in actuarial survival (X2 = 9.533, p = 0.002). The distant relapses in arms 2 and 3 occurred at significantly shorter times after diagnosis than those in arm 1 (t = 4.1083, p = 0.0001). Postponement of radiation therapy by chemotherapy might have accounted for the earlier distant relapses in arm 2 and 3. Radiation therapy alone given in radical dose had been demonstrated to achieve significantly more complete responses in cervical nodal metastases than either forms of chemotherapy (VBMF or PVBMF) given just two courses prior to radiation therapy (p less than 0.00003). More controlled clinical trials must be completed before acceptance of chemotherapy as part of a standard radical treatment for advanced nasopharyngeal carcinoma with advanced cervical lymph nodal metastases. In all future trials, closer integration in time sequence between the two treatment modalities is indicated. Meanwhile cervical nodal status (CR vs, PR plus NR) at the end of any treatment was shown to be of paramount prognostic significance.

Treatment of stage I nasopharyngeal carcinoma: analysis of the patterns of relapse and the results of withholding elective neck irradiation.

This is a retrospective analysis of 196 patients with nasopharyngeal carcinoma Stage I (Ho's classification) treated by megavoltage radiation during 1980-1984. The primary target volume included all potential sites of local invasion and the first station lymph nodes at retropharyngeal spaces. Two different dose schedules were used, both gave a total tumor dose biologically equivalent to 65 Gy by conventional fractionation, and both achieved a 5-year actuarial local-recurrence-free survival of 88%. Elective neck irradiation was withheld in all except seven patients. The overall 7-year actuarial survival was 85%, but the relapse-free survival was only 62%. The patterns of relapse, prognostic factors, and treatment complications were analyzed. Eighteen patients (9%) recurred locally. Radical retreatment with radiation achieved complete remission in seven out of fifteen cases. Distant failure occurred in 17 patients (9%). Although 57 (30%) of the 189 patients without elective neck irradiation subsequently showed lymph node involvement, none of the seven regionally-treated patients relapsed. The successful regional salvage rate was 81% overall (46 out of 57 patients), but 90% (44 of 49) for those properly treated with whole neck irradiation. However, the 7-year actuarial survival was lower in patients with nodal relapse than those without (70% versus 87%) because of the associated higher incidence of hematogenous dissemination. The various aspects of treatment, the value of elective neck irradiation in particular, are discussed.

Prognosis and histology in Stage I nasopharyngeal carcinoma (NPC).

During 1969-1975, 212 new patients with Stage I nasopharyngeal carcinoma (NPC) with a tumor apparently confined to the nasopharynx were treated at Queen Elizabeth Hospital, Kowloon, Hong Kong. The initial histologies of 137 patients were available for review and further studies. The primary tumors were histologically classified into two major types--squamous cell carcinoma (35 patients) and undifferentiated carcinoma (102 patients). The latter was further divided into 4 sub-types: lymphoepithelioma of the Schmincke type, lymphoepithelioma of the Regaud type, spindle cell carcinoma, and undifferentiated carcinoma of the nasopharyngeal type. Such histological typing of the initial tumor was not of value in predicting the clinical outcome, whether in terms of 5-year crude or disease-free survival rate, or the tendency of the tumor to develop recurrence at the primary site, or distant metastases after a standardized course of radiation therapy. There is no significant correlation between the extent of mononuclear infiltration nor fibrosis in the tumor stroma and the survival or tumor control rates.

Symptomatic hypothalamic-pituitary dysfunction in nasopharyngeal carcinoma patients following radiation therapy: a retrospective study.

Endocrine assessment was performed in 32 relapse-free southern Chinese patients (21 males and 11 females, aged 27-50 years at the time of assessment) 5-17 years following radiation therapy (RT) alone for early nasopharyngeal carcinoma (NPC). Initial screening was done using questionnaires emphasizing on impaired sexual function and menstrual disturbance plus measurement of serum levels of thyroxine, free thyroxine index, thyrotropic hormone, prolactin, and additionally testosterone for males only. Those showing abnormalities were subjected to detailed pituitary function tests. Hypothalamic-pituitary dysfunction was found in 7 female patients and only 1 male patient. A delayed TSH response to thyrotropin releasing hormone suggesting a hypothalamic disorder was seen in 6 of the affected female patients, and hyperprolactinaemia in also 6. None of the patients had evidence of diabetes insipidus. Hypopituitarism became symptomatic 2-5 years after RT with a mean latent interval of 3.8 years. A practical protocol for regular endocrine assessment for NPC patients after RT has been proposed. Multiple linear regression analysis of the radiotherapeutic data from the 11 female patients indicates that the likelihood of late occurrence of symptomatic hypothalamic-pituitary dysfunction following RT is dependent on the TDF of the target dose to the nasopharyngeal region and the height of the upper margin of the opposed lateral facial fields above the diaphragma sellae (coefficient of multiple correlation = 0.9025). Except when the sphenoid sinus or the middle cranial fossa is involved, it is advisable to set the height of the upper margin of the lateral facial field at a level no higher than the diaphragma sellae. The hypothalamus and possibly the pituitary stalk as well may sustain permanent damage by doses of radiation within the conventional radiotherapeutic range for carcinomas.

Retrospective analysis of patients with nasopharyngeal carcinoma treated during 1976-1985: survival after local recurrence.

PURPOSE: To study the value of re-irradiation, the overall survival and pattern of failures for patients with nasopharyngeal recurrence. METHODS AND MATERIALS: All the 891 patients with local recurrence following radiotherapy for nasopharyngeal carcinoma during 1976-1981 were retrospectively analyzed. Only 70% of them had local failure alone at the time of detection, and the T-stage distribution (by Ho's system) was 31% rT1, 16% rT2, 51% rT3, and 1% rT?. Seven hundred and six (79%) patients had been re-irradiated with various techniques and doses. Among those who failed, 50 had further irradiation. RESULTS: The overall 5- and 10-year actuarial cancer-specific survival rates were 14% and 9%, respectively. Patients with rT3 disease had the worst prognosis. Successful local salvage was achieved in 32% of those re-irradiated (26% of the whole series). The highest control rate was achieved by those treated with external radiotherapy to 60 Gy (equivalent) or above. Only 8/50 patients responded to the third course of radiotherapy. The cumulative incidence of late post-re-irradiation sequelae was 24%, and the treatment mortality rate 1.8%. Besides local failure, 54% had regional relapse and/or distant metastasis. Thus, only 16% of recurrent patients were totally disease-free at final assessment. CONCLUSION: The overall prognosis for patients with nasopharyngeal recurrence was grave. High dose re-irradiation could achieve successful local salvage in a substantial number of patients with early recurrence, but late complications did occur. Furthermore, high incidence of failure at other sites was observed.

Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of failure.

This is a retrospective analysis of 5037 patients with squamous cell carcinoma of the nasopharynx treated during the years 1976-1985. The stage distribution according to Ho's classification was 9% Stage I, 13% II, 50% III, 22% IV, and 6% Stage V. Only 4488 (89%) patients had a full course of megavoltage radiation therapy. The median equivalent dose to the nasopharyngeal region was 65 Gy and cervical region in node-positive patients 53 Gy. Seventy percent (906/1290) of the node-negative patients had no prophylactic neck irradiation. The overall actuarial 10-year survival rate was 43%, and the corresponding failure-free survival 34%. Altogether, 4157 (83%) patients achieved complete remission lasting more than 6 months, but 53% (2205/4157) of them relapsed after a median interval of 1.4 years. The 10-year actuarial local, regional, and distant failure-free rates were 61%, 64%, and 59%, respectively. Thirty-eight percent (338/891) of all patients with local recurrence achieved second local remission. The local complete remission rate with aggressive re-irradiation alone was 47% (333/706). But 37% (124/338) of the responders recurred the second time. The incidence of distant failure correlated significantly with both the N-stage and the T-stage, with the highest (57%) occurring in patients with N3 disease. The incidence of nodal relapse in node-negative patients was 11% (44/384) among those given prophylactic neck irradiation, but 40% (362/906) among those without. Therapeutic irradiation achieved a complete regional remission rate of 90% (306/339). However, despite successful salvage, these patients had a significantly higher distant failure rate than those without nodal relapse, even if they remained local-failure-free (21% vs 6%). Patients treated during 1981-1985 achieved significantly better treatment results than those treated during 1976-1980, especially in terms of the overall survival (57% vs 47% at 5-year), the overall failure-free survival (42% vs 35% at 5-year), and the local failure-free rate (70% vs 63% at 5-year). The possible contributing factors are discussed.

Total biological effect on late reactive tissues following reirradiation for recurrent nasopharyngeal carcinoma.

PURPOSE: To assess the additional damage of normal tissues attributable to reirradiation and the magnitude of partial recovery following the initial course. METHODS AND MATERIALS: Symptomatic late complication rates (excluding xerostomia) in 3635 patients receiving one course (Group 1) and 487 patients receiving two courses of external radiotherapy (Group 2) for nasopharyngeal carcinoma were retrospectively analyzed and compared. RESULTS: Group 2 had significantly lower actuarial complication-free survival rates than Group 1: 48% versus 81% at 5 years. The post-retreatment incidence was significantly affected by biologically effective dose (BED) (assuming an alpha/beta ratio of 3 Gy) of the first course: hazard ratio (HR) = 1.04 per Gy(3) (p = 0.01), but only marginally by that of the second course: HR = 1.01 per Gy(3) (p = 0.06). If the summated BED was taken as the dose unit, it was estimated that a total BED of 143 Gy(3) would induce a 20% incidence at 5 years, while the corresponding dose projected from Group 1 was 111 Gy(3). The gap effect was insignificant in the overall analyses, but a trend of decreasing risk with increasing interval was observed in patients with gap > or = 2 years: HR = 0.86 per year (p = 0.07). CONCLUSION: The major determinant of post-retreatment complication is the severity of damage during the initial course. The sum of total doses tolerated is higher than that expected with a single-course treatment, suggesting occurrence of partial recovery (particularly in those reirradiated after an interval of 2 years or more).

T1 nasopharyngeal carcinoma: the effect of waiting time on tumor control.

PURPOSE: To study the effect of unperturbed tumor growth on the control of nasopharyngeal carcinoma. METHODS AND MATERIALS: This is a retrospective analysis of 290 patients with T1N0-3M0 disease (Ho's classification) treated by the same technique and dose schedule to the nasopharyngeal region. The median interval from diagnosis to commencement of irradiation was 26 days (range: 8-68 days). Cox proportional hazards analyses were performed to study the independent effect of waiting time on the probability of failure at various sites. Actuarial failure-free survival of patients with delay < 22 days, 22-28 days and > 28 days were also compared to illustrate the clinical observation. RESULTS: Both tests showed that waiting time had no significant impact on local failure: The N-stage stratified hazard ratio was 0.985 per day, and the 10-year local failure-free survival for the three groups was 76%, 80%, and 82%, respectively. A similar result was obtained for nodal control in patients with our scheduled neck irradiation. Although the p value of all tests failed to reach statistical significance, the N-stage stratified hazard ratio for distant failure was 1.020 per day, and the corresponding metastasis-free survival in patients with N2-3 disease was 70%, 65%, and 52%, respectively. For node-negative patients without elective neck irradiation, the hazard ratio was 1.019 per day, with the corresponding regional failure-free rates at 57%, 62%, and 33%, respectively. CONCLUSION: Delay in initiation of treatment to the primary target (within the range observed) did not affect the control rate at irradiated sites, but there was a trend (though statistically insignificant) towards increase in failures at untreated sites that were clinically too serious to be ignored.

Recurrent nasopharyngeal carcinoma: the puzzles of long latency.

PURPOSE: To study the peculiar characteristics of relapses with long latency following radical treatment for nasopharyngeal carcinoma. METHODS AND MATERIALS: 847 patients with nasopharyngeal recurrence were retrospectively studied, focusing on the independent effects of latency on different outcome aspects and its relationship with other prognostic factors. RESULTS: The proportion of recurrence with latency <2 years (Group A), 2-<5 years (Group B), and 25 years (Group C) were 52%, 39%, and 9%, respectively. A higher proportion of Group C originated from patients with node-negative early primary, but fewer of them were still confined within the nasopharynx at detection of recurrence. There was no significant difference in the choice of salvage modality, but among those reirradiated, more of Group C were treated with external beams to a higher dose. The difference in local salvage rate was not statistically significant, but the 5-year distant failure-free rates of the 3 groups were 57%, 67%, and 83%, respectively; and the corresponding disease-specific survival (DSS) were 14%, 20%, and 35%. Multivariate analysis confirmed the independent significance of latency in predicting distant failure (hazard ratio = 0.81 per year, p < 0.01) and cancer deaths (hazard ratio = 0.90 per year, p < 0.01). CONCLUSIONS: Nasopharyngeal recurrence with long latency showed different natural behavior: the prognosis was significantly better due to lower risk of distant failure.

Effect of time, dose, and fractionation on temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models. METHODS AND MATERIALS: Consecutive patients (1008) treated radically with four different fractionation schedules during 1976-1985 for T1 nasopharyngeal carcinoma were retrospectively analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18-84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5-4.2 Gy, total dose 45.6-60 Gy, and overall time 38-75 days. RESULTS: Despite a lower total dose of 50.4 Gy, the 621 patients irradiated with 4.2 Gy per fraction had a significantly higher incidence of temporal lobe necrosis than the 320 patients treated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidence being 18.6% vs. 4.6%, p < 0.001. Multivariate survival analysis showed that fractional effect (product of total dose and fractional dose) was the most significant factor: p = 0.0022, hazard ratio (HR) = 1.044 per Gy2. Overall time and age were both insignificant. The alpha/beta ratio calculated from our data was 2.9 Gy (95% CI: -1.8, 7.6 Gy). Biological effective dose (BED(Gy3)), neuret, and brain tolerance unit all showed strongly significant correlation with the necrotic rate (p < 0.001), and gave similar predictions. The hazard of TLN increased by 14% per Gy3, and it was estimated that 64 Gy (at conventional fractionation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. Not only did the nominal standard dose (NSD) show the lowest value in terms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates. CONCLUSION: Fractional effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assuming an alpha/beta ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misleading predictions.

A proposed modification of the Ho stage-classification for nasopharyngeal carcinoma.

Based on the clinical data of a retrospective study of 659 NPC patients with routine computed tomography of the nasopharyngeal region, a refinement of Ho's stage-classification for NPC is proposed with reduction in the number of overall stages without sacrificing the accuracy in predicting prognosis in the short term. Classifying the cervical lymph nodal metastasis into supraclavicular (Ho's N3) and above supraclavicular (Ho's N1 + N2) and the nasopharyngeal primary into early (Ho's T1 + T2n + T20) and advanced (Ho's T2p + T3 + T3p) forms the conceptual backbone of the present proposed modification of the original Ho stage-classification. Power in predicting the occurrence of distant metastases and the local failures has been enhanced by the proposed T-stage and N-stage re-grouping. Retrospective comparison between Ho's and the UICC stage-classifications showed a more even patients number distribution among the overall stages and a greater power in predicting NPC prognosis for the former. Prospective studies to compare the value of the different stage-classifications are required for recommendation of a single classification for general acceptance to facilitate comparison of treatment results between centres.

Malignant lymphoepithelial lesion of the salivary gland.

Eight cases of malignant lymphoepithelial lesion (MLEL) of major salivary glands, seven of which occurred in Southern Chinese patients, are reported. All but two of the patients were older than 40 years of age; there were five male and three female patients. The parotid and submandibular glands were the sites of origin in equal numbers of cases. Six patients had elevated titers of serum IgA against Epstein-Barr virus capsid antigen. Seven remained well after surgery and local radiation therapy, and one died of miliary tuberculosis without evidence of residual neoplasm. Histologically, MLELs were characterized by syncytial clumps of large cells with vesicular nuclei and prominent nucleoli, admixed with abundant small lymphocytes and plasma cells. Two features not emphasized previously in the literature were the presence of reactive histiocytes in some epithelial islands, producing a starry sky pattern, and perineural invasion, which was identified in four cases. The tumor cells showed strong immunostaining for cytokeratin. The literature concerning this rare tumor is reviewed, and the differential diagnosis between MLEL and benign lymphoepithelial lesion, metastatic undifferentiated carcinoma, and malignant lymphoma is discussed.

Diet as a confounder of the association between air pollution and female lung cancer: Hong Kong studies on exposures to environmental tobacco smoke, incense, and cooking fumes as examples.

Chinese females in Hong Kong, where only about a third of the lung cancer cases can be attributed to a history of active smoking, have a world age-standardized lung cancer incidence rate of 32.6 per 100 000, which is among the highest in the world. Trends in Hong Kong's female lung cancer mortality also indicate a tripling in mortality rates from 1961 to 1990. The characteristically high Chinese female lung cancer incidence among nonsmokers is also found among overseas Chinese communities in Singapore and Hawaii. To help elucidate the role of ingested and inhaled substances in the etiology of lung cancer, four epidemiological studies have been conducted in Hong Kong over the last 15 years: (1) a retrospective study of 200 cases and 200 neighbourhood controls, (2) a cross-sectional study measuring personal exposures to nitrogen dioxide among 362 children and their mothers, (3) a site monitoring study of 33 homes measuring airborne carcinogens, and (4) a telephone survey of 500 women on their dietary habits and exposure to air pollutants. Selected data from each study were drawn to evaluate exposures to three major air pollutants (environmental tobacco smoke, incense, and cooking fumes), their relationship with lung cancer risk, and their association with dietary habits. Generally in this population, nutritionally poorer diets were characterized by higher consumption of alcohol and preserved/cured foods, whereas better diets were characterized by higher intakes of fresh fruits, vegetables, and fish. For environmental tobacco smoke, exposure was only moderately high in Hong Kong (36% have current smokers at home), lung cancer risk was equivocal with exposure, and it was associated with poorer diets among wives with smoking husbands. Incense was identified as a major source of exposure to nitrogen dioxide and airborne carcinogens, but it had no effect on lung cancer risk among nonsmokers and significantly reduced risk (trend, P-value = 0.01) among smokers, even after adjusting for smoking. The last finding may be explained by the relatively better diets among smoking women who burned incense versus those who did not. Although about 94% of the Chinese women cook on a regular basis, and the cooking fires were associated with increased airborne carcinogens, nonsmoking women who cooked for more than 25 years had a 60% reduction in lung cancer risk and the trend was highly significant (P < 0.001). Again, this unexpected finding may be due to the confounding effects of diet. Female controls who cooked for more than 25 years had a poorer diet than those who cooked for shorter durations. These three examples were chosen to illustrate the complexities of assessing air pollution exposure, and understanding the behavioral and dietary dynamics underlying lung cancer risk assessments. Our conclusion is that diet can be an important confounding factor affecting lung cancer risk estimates from air pollution exposures among Chinese women living in an affluent urban environment.

Worldwide epidemiological patterns of lung cancer in nonsmokers.

A review of published reports on lung cancer was done to describe its worldwide epidemiological pattern and to elucidate the contribution of smoking and nonsmoking risk factors in its aetiology. Among lung cancer patients, roughly 98% of males worldwide, and 70-90% of European and American females, reported a history of smoking. Asian women had much lower (6-57%) rates of smoking. Mortality rates among female nonsmokers showed about a four-fold difference, being lowest in India and Japan, intermediate in the USA, and highest among the Chinese. There was some indication that incidence rates among nonsmokers may have increased in some societies in this century. The usefulness of histological comparisons among nonsmokers seemed limited since its distribution did not vary by place or ethnicity; about 70% were adenocarcinomas. In Western populations, younger lung cancer patients were more likely to have been smokers, whereas the opposite was true in Asian populations. Thus the epidemiological patterns of lung cancer in Western and non-Western societies are likely to be different, with nonsmoking risk factors being more important among women in general, and Asian women in particular.

Proton-assisted switching of reaction pathways of stilbene analogues brought by direct irradiation.

[figure: see text] Photochemical reaction pathways during direct irradiation of stilbene analogues (1a-1d) can be switched completely by adjusting the concentration of hydrochloric acids. Competitive ring opening and acid-catalyzed hydrolysis processes are responsible for this novel selectivity.