Study of the naturally occurring radionuclide Beryllium-7 (Be-7) in Hong Kong.

Beryllium-7 (Be-7) is one of the naturally occurring radionuclides being monitored under the Global Atmosphere Watch Programme of the World Meteorological Organization. Be-7 mainly originates from cosmic rays. It can be used as a tracer to facilitate understanding of the atmospheric vertical transport by observing its spatial and temporal distribution characteristics. The Hong Kong Observatory has been operating an environmental radiation monitoring programme for decades, and long record of Be-7 activity concentration data in airborne particulate samples are available to characterize the behaviour of Be-7 in the lower atmosphere in Hong Kong. In this study, Be-7 activity concentration data of airborne particulates collected at three locations in Hong Kong from 1993 to 2020 are examined. Temporal variations are analyzed. In particular, the long-term monthly average Be-7 activity concentrations are found to be most sensitive to precipitation. The relevant data analysis, as well as key factors affecting the Be-7 activity concentrations in the lower atmosphere in Hong Kong, will be described.

A young woman with hypogonadism, hypertension and hypokalaemia.

We report a case of a 16 years old girl who presented sequentially with primary amenorrhoea, hypertension and hypokalaemia. Eight years later, she was finally diagnosed with 17alpha-hydroxylase deficiency congenital adrenal hyperplasia. Previous antihypertensive medications were stopped. Hydrocortisone alone successfully maintained normotension and normokalaemia.

Purification and characterization of human macrophage-derived granulomonopoietic enhancing factor (GM-EF).

A granulomonopoietic enhancing factor (GM-EF) capable of promoting the effect of colony-stimulating factors (CSFs) on myeloid progenitor cells has been purified to homogeneity from serum-free medium conditioned by fully mature human macrophages. GM-EF was a glycoprotein with an apparent molecular weight of 74 kd and an isoelectric point of 5.2-5.3. The purified protein was heat stable (75 degrees C for 30 min) and was sensitive to treatment with trypsin, papain, and bacterial protease but not to neuraminidase. The activity of GM-EF could be effectively neutralized by GM-EF-specific antiserum, and no antigenic cross-reactivity was observed using antisera against interleukin (IL)-1, IL-4, and IL-6. These results suggest that GM-EF is a unique cytokine that is different biochemically and antigenically from other hematopoietic enhancing factors such as IL-1, IL-4, and IL-6.

The effect of lipopolysaccharide on the production of GM-EA, GM-CSA, and PGE2 by human monocyte-derived lipid-containing macrophages.

Monocyte-derived lipid-containing macrophage (MDLM) was the major source of granulomonopoietic enhancing activity (GM-EA) but these well-differentiated cells were unable to synthesize constitutively the granulocyte-macrophage colony-stimulating activity (GM-CSA) that was contributed mostly by the younger monocytoid cells. The presence of various concentrations (0.5-10 micrograms/ml) of lipopolysaccharide (LPS) potentiated the production of GM-EA by MDLM. Enhancement of GM-EA production peaked at about 0.5 micrograms/ml of LPS, but at higher doses (10-40 micrograms/ml) LPS became suppressive. In parallel, LPS-induced production of prostaglandin E2 (PGE2) was observable only at higher doses (10-40 micrograms/ml), suggesting a correlation between PGE2 production and LPS-mediated suppression of GM-EA synthesis. At optimal concentration (0.5 micrograms/ml), LPS could effectively override the inhibitory effect of interferon-gamma on the production of GM-EA. In addition, GM-CSA production by MDLM can be partly restored by stimulation with high doses of LPS (10-40 micrograms/ml). These results suggest that MDLMs have functional potentials similar to the younger macrophages and may play an important role in the regulation of myelopoiesis through the release of GM-EA and related regulators.

Bone marrow transplantation for severe aplastic anemia--a study of twenty-one Chinese patients in Taiwan.

A total of 21 multiply transfused patients with severe aplastic anemia (SAA) were treated with bone marrow transplantation between March 1985 and September 1990: 20 allogeneic and one syngeneic transplants. A positive response in mixed lymphocyte culture (MLC) was also noted in 7 allogeneic recipients. Pregraft conditioning included high-dose cyclophosphamide (CY) 200 mg/kg over 4 consecutive days, followed by 300 cGy total-body irradiation the day before BMT. Seventeen patients older than 14 years received additional donor buffy-coat cells infusion for 5 days posttransplant. A combination of methotrexate and cyclosporine was used for prophylaxis of graft-versus-host disease. Seventeen patients were alive with a functional graft, and Kaplan-Meier product limit estimates showed a 80.95% probability of survival at 67.7 months. There were 4 deaths: two died of primary graft failure, one from secondary rejection, and the other from chronic GVHD-related complications. Acute GVHD, grade I was noted in only one patient (5.6%). In contrast, chronic GVHD was observed in 10 out of 18 (55.6%) evaluable patients. Venoocclusive liver disease and interstitial pneumonitis were not diagnosed. Our findings indicate that the combination of CY/TBI/BC is well tolerated and results in a low incidence of graft failure/rejection in multiply transfused Chinese patients who received transplants for SAA. The MTX/CsA combination was confirmed as being remarkable in reducing the incidence and severity of acute GVHD. For patients with SAA under the age of 40, with an HLA-identical sibling, we highly recommend BMT as the treatment of choice.

Allogeneic peripheral blood progenitor cell transplant after bone marrow graft failure: report of a case.

A 31-year-old woman diagnosed with acute myelocytic leukemia received an allogeneic peripheral blood progenitor cell (PBPC) transplant one month after a previous bone marrow graft failed. PBPCs were mobilized with granulocyte-colony-stimulating factor and collected by apheresis. T-cell depletion was not performed and no further chemo- or radiotherapy was given for the second transplant. Engraftment was prompt, with the peripheral blood leukocyte count rising dramatically to 2,400/microL, six days after completion of PBPC transplant. The platelet count reached 36,000/microL on the eighth day and was self-sustained thereafter. Both blood grouping and bone marrow karyotyping confirmed donor origin of the engraftment. At the time of writing, the patient has been disease-free for over 200 days without any complications of acute or chronic graft-versus-host disease.

Allogeneic peripheral blood stem cell transplantation and early detection of donor engraftment by polymerase chain reaction.

Patients with hematologic malignancy or severe aplastic anemia after myeloablative chemo- and radiotherapy were given granulocyte colony-stimulating factor (G-CSF)-mobilized, cryopreserved allogeneic peripheral blood stem cells (PBSCs) from 15 healthy donors who were either human leukocyte antigen (HLA)-matched siblings (n = 13) or haploidentical offspring (2). Polymerase chain reaction-amplified short tandem repeat genotyping was used for early confirmation of donor engraftment after PBSC transplantation (PBSCT). A standard cyclosporine A/methotrexate combination was used to prevent acute graft-versus-host disease (GVHD). All donors, including one in the third trimester of pregnancy, tolerated G-CSF administration and 3-day PBSC harvesting procedures well. Engraftment was prompt for all patients; it was verified using a panel of 12 human polymorphic short tandem repeat loci from bone marrow as early as 7 days posttransplantation. This status was maintained until relapse, when mixed chimerism was detected using the polymerase chain reaction. A minimum resurgence of recipient cells to 1% of the population was required to detect chimerism. The median times to recovery of the absolute neutrophil count to greater than 0.5 x 10(9)/L and the sustained platelet count to greater than 20 x 10(9)/L without transfusion were 10 and 12 days after PBSCT, respectively. Six patients experienced acute GVHD, Grade I in two patients and Grade II in four, including two HLA-haploidentical recipients. Chronic GVHD was noticed in three of the 11 patients who were followed for at least 100 days after PBSCT. Ten patients were still alive at the latest follow-up and have been disease free for a median of 278 days (range 60-671). Five patients died from causes other than graft failure: three from leukemia relapse and two from transplant-related complications. The results confirm that G-CSF can be safely administered to healthy donors and that engraftment after allogeneic PBSCT is fast and durable. Complete chimerism can be detected early by genomic analysis. PBSCT may offer an alternative to bone marrow transplantation.

Influence of gamma irradiation and storage on apheresis platelets.

BACKGROUND AND PURPOSE: Gamma irradiation of platelet concentrates to prevent graft-versus-host disease may inactivate contaminated lymphocytes and subsequently inhibit the synthesis of cytokines in the apheresis platelets during storage. We investigated the influence of irradiation and storage on apheresis platelets collected with the COBE Spectra or Fenwal CS-3000 Plus systems. METHODS: Eleven units of apheresis platelets were collected with a COBE Spectra cell separator and another 11 units with a Fenwal CS-3000 Plus system. Each unit of apheresis platelets was divided into two equal parts: one was irradiated with 3000 cGy directly after blood donation, and the other served as a control. Cell counts, platelet activation marker CD62 antigen, blood gas values, and supernatant concentrations of K+, Na+, lactate, glucose, interleukin-1 beta (IL-1 beta), IL-8, and tumor necrosis factor-alpha (TNF-alpha) were determined in paired samples on the day of collection (day 0) and after 5 days of storage (day 5). RESULTS: No significant differences in white cell counts or TNF-alpha concentrations were noted between the irradiated and control platelets on day 0 or day 5, whereas the mean proportion of platelets expressing CD62P (22.65% vs 25%, p = 0.014) and the mean IL-1 beta (45.55 pg/mL vs 52.75 pg/mL, p = 0.004) and IL-8 concentrations (10.68 pg/mL vs 13.07 pg/mL, p = 0.015) were significantly lower in irradiated than control platelets on day 5. The 5-day storage significantly increased the mean proportion of platelets expressing CD62P (25.00% vs 15.02%, p = 0.008), mean PO2 (116.34 mm Hg vs 98.07 mm Hg, p = 0.002), and mean concentrations of K+ (3.30 mmol/L vs 3.06 mmol/L, p < 0.001), lactate (15.12 mmol/L vs 3.23 mmol/L, p < 0.001), IL-1 beta (52.75 pg/mL vs 29.73 pg/mL, p = 0.001), and IL-8 (13.07 pg/mL vs 3.62 pg/mL, p < 0.001). Five-day storage also significantly decreased white cell count (0.18 x 10(8) vs 0.74 x 10(8), p < 0.001), PCO2 (19.38 mm Hg vs 50.51 mm Hg, p < 0.001), and concentrations of HCO3- (10.36 mmol/L vs 21.34 mmol/L, p < 0.001) and glucose (193.37 mg/dL vs 309.18 mg/dL, p < 0.001). Platelet counts and concentrations of IL-1 beta, IL-8, and TNF-alpha on day 0 did not differ significantly between control apheresis platelets collected with the Fenwal CS-3000 Plus and those collected with COBE Spectra. The mean white cell count (1.29 x 10(8) vs 0.19 x 10(8), p = 0.002) and the proportion of platelets expressing CD62P (24.71% vs 7.09%, p < 0.001) on day 0, however, were significantly higher in the platelets collected with the Fenwal CS3000-Plus than in those collected with the COBE Spectra. CONCLUSIONS: Gamma irradiation of apheresis platelets inhibits the expression of platelet CD62P and the secretion of IL-1 beta and IL-8 after 5 days' storage.

Varicella zoster virus infection after allogeneic or autologous hemopoietic stem cell transplantation.

A retrospective study was carried out in 161 patients who underwent allogeneic or autologous hemopoietic stem cell transplants. The aim was to determine the frequency, outcome and risk-factors associated with varicella zoster virus (VZV) infection. Post-transplant VZV infection occurred in 29 patients. The median onset of infection was 6.5 months post-transplant, with 82% of cases occurring within the first year. Localized herpes zoster was seen in 27 patients, one patient had varicella, and one patient had simultaneous presentation of both herpes zoster and varicella. No cutaneous or visceral dissemination was noted in the series. Each patient was treated with intravenous acyclovir. Mild complications with postherpetic neuralgia were reported by three patients. There were no deaths from VZV infection. Two risk factors noted to be associated with VZV infection were the presence of graft-versus-host disease in allogeneic transplants and leukemia as the underlying disease in autologous transplants. The overall incidence of post-transplant VZV infection in the present series was relatively low compared with that of other reports involving either allogeneic or autologous bone marrow transplantation.

Polymorphisms of twelve short tandem repeat loci in a Taiwanese population and their application in parentage testing.

With the advancement of techniques in molecular biology, rapid, sensitive, and reliable methods of DNA typing for parentage testing have become available. In this study, we evaluated the usefulness of multiplex polymerase chain reaction (PCR) with 12 unlinked short tandem repeat (STR) loci for paternity testing in Taiwan. The genetic informativeness of this test was then compared with that of conventional human leukocyte antigen (HLA) analysis in 167 parentage studies. The 12 STR loci alone provided a cumulative power of exclusion of up to 0.9998. Paternity was excluded in 59 (35.3%) cases, including 40 of 112 paternity trios and 19 of 55 paternity duos. In the 40 trios in which paternity was excluded, a mean of 6 (range, 3-9) incompatible STR markers were in the 19 duos in which paternity was excluded, a mean of 4 (range, 1-8) incompatible STR markers were noted. In the 72 trios in which the alleged paternity could not be excluded, the mean probabilities of paternity (PP) were 90.6863% with HLA testing alone, 99.9847% with STR analysis alone, and 99.9972% with combined HLA and STR analysis. In the 36 duos in which the alleged paternity could not be excluded, the mean PPs were 81.4768% with HLA testing alone, 99.6124% with STR analysis alone, and 99.9145% with combined HLA and STR analysis. These results suggest that STR analysis is very powerful when used alone for paternity trio testing and when combined with conventional serologic HLA typing for duo parentage testing in the Taiwan population.

The value of gametoclonal variation in breeding for quantitative traits in flue-cured tobacco (Nicotiana tabacum L.).

In tobacco (Nicotiana tabacum L.), anther-derived doubled haploid populations have been shown to exhibit large amounts of unexpected genetic variation and a severe depression in cured leaf yield when compared to conventionally inbred genotypes from comparable sources. A previous study had predicted that the yield depression observed in a doubled haploid population-derived from a near homozygous cultivar, NC95, might be overcome through a recurrent selection program. In the current study, progress from three cycles of full-sib family selection for improved yield in an anther-culture derived population of NC95 was measured, as well as the remaining genetic variation within the population. A design II experiment was conducted in the population following three cycles of selection. Results indicate that the NC95 yield level has been recovered in the third selection cycle population. Although most of the genetic variation in the population appears to be exhausted, the additive genetic variance among maternal half-sib families for yield is significant, and it appears that continued yield improvement can be made through recurrent selection. Significant additive-genetic variance for yield was found among maternal half-sib families but was essentially zero among the paternal half-sib families, suggesting that remaining genetic variation is not being transmitted through pollen. One possible explanation results from the phenomenon of DNA amplification that can occur during the anther culture process, and that may enable extraordinary recombinational events and reduce the viability of male gametes.

Factors affecting progenitor cell yields using three tandem leukaphereses in previously treated malignancies.

BACKGROUND: Mobilized peripheral blood progenitor cells (PBPCs) have increasingly been used to replace autologous bone marrow to allow faster hematopoietic reconstitution after myeloablative therapy in various malignancies. There is a paucity of data concerning factors that affect the total yield of three tandem leukaphereses. METHODS: Factors affecting the yield of PBPCs were analyzed in a series of 121 consecutive patients including 36 with non-Hodgkin's lymphoma, two with Hodgkin's disease, four with multiple myeloma, 44 with acute leukemia, 20 with breast cancer and 15 with other solid tumors. PBPCs were mobilized using granulocyte-colony-stimulating factor (G-CSF) alone (group I, n = 15), or after conventional-dose (group II, n = 70) or high-dose (group III, n = 36) chemotherapy followed by G-CSF. The total yield of three tandem PBPC collections for each patient was assessed by the number of mononuclear cells (MNCs), CD34+ cells and colony-forming units of granulocyte macrophages (CFU-GM). The factors evaluated included age, sex, diagnosis, history of marrow involvement, previous radiotherapy, the number of prior chemotherapy cycles and mobilization method. The two -sample t-test and logistic regression analysis were performed for univariate and multivariate analysis, respectively. RESULTS: With univariate analysis, a diagnosis of acute leukemia, positive history of bone marrow involvement, more chemotherapy cycles and mobilization with high-dose chemotherapy adversely affected the yields of CD34+ cells. By multivariate analysis, Group II had higher yields of MNCs (p = 0.039), CFU-GM (p = 0.002) and CD34+ cells (p = 0.011) than Group III. Fewer cycles of prior chemotherapy is the common favorable factor for the yields of both CD34+ cells (p = 0.016) and CFU-GM (p = 0.017). CONCLUSIONS: The number of prior chemotherapy cycles adversely affects progenitor cell yield. Conventional-dose chemotherapy followed by G-CSF seems to be the mobilization methods of choice for heavily pretreated cancer patients with limited bone marrow reserve. PBPCs should be harvested early, when the tumor burden is less, to avoid cumulative marrow toxicity from chemotherapy.

Hemolysis after ABO-incompatible platelet transfusions.

An 18 year old girl, with acute myeloid leukemia, developed progressive hemolysis after receiving multiple transfusions with ABO-incompatible platelets. It was caused by passive transfusion of anti-A and -B isoagglutinin from the donor plasma. Her hemoglobin level returned to normal after giving group compatible or pooled and reduced volume platelet concentrates. Transfusing group-incompatible platelets is not contraindicated, but donor plasma reduction should be considered for those patients who need prolonged platelet support. Testing for isoagglutinin titer in group O donors is an alternate method to reduce the incidence of plasma-induced hemolysis in group-incompatible platelet transfusions.

Family study of Rh haplotype frequencies in Taiwan.

Two hundred and two families (404 parents and 448 children) were typed for Rh antigens. The most common Rh haplotype is R1R1 followed by R1R2 and R1r. R1r', R2r', R0r', R0r and r'r are all very rare. The results of observed and expected haplotype frequencies do not differ significantly except few rare phenotypes. However, there are some major differences between Caucasian and Chinese populations in certain Rh genotypes. Although r is the second common genotype in Rh system among Caucasian but is rather rare in Chinese.

HLA haplotype frequencies of Taiwan-Chinese families.

HLA haplotype frequency was studied by typing 201 members of 32 unrelated families. Linkage disequilibrium was determined by observed and expected haplotype frequencies. The two-locus haplotype frequencies with most significant linkage disequilibrium were A30-B13, Aw33-B17, Bw46-Cw11, B12-Cw8, A1-Cw6 and A33-Cw3. No locus recombination was noted among 137 children.

Clinical application of therapeutic hemapheresis.

Hemapheresis has been used in a variety of clinical states, primarily for its ability to remove an offending component, likely be either plasma or cellular elements. We have reviewed 43 cases of therapeutic hemapheresis over the past two years at Veterans General Hospital. There were 20 cases of plasmapheresis, 7 cases of leukapheresis and 16 cases of thrombocytapheresis. Most of them had satisfactory and desirable effects except a few cases in therapeutic plasmapheresis. Among 20 cases of therapeutic plasmapheresis, all but 2 cases of systemic lupus erythrematosus had transient clinical improvement. Average decrease of leukocyte count in 11 procedures of leukemic patients was 37%. As for the myeloproliferative disorders with thrombocytosis, the average drop of platelet count was 41%. The side effects of therapeutic hemapheresis were not infrequent. There were 56 recorded side effects with one sudden death among 94 procedures. Hemapheresis is useful in certain clinical conditions but more judicious application should be considered.

Iron overload in untransfused patients with hemoglobin H disease.

Two Chinese patients with hemoglobin (Hb) H disease without a history of blood transfusion developed iron overload at the age of 45 and 53 years, respectively. Human leukocyte antigen (HLA) system types of these 2 patients were A19, A11, B13, B62 and A2, A24, BW55, respectively, which are not related to the common haplotypes for idiopathic hemochromatosis. Since severe iron loading is a rare clinical manifestation in untransfused patients with Hb H disease, the iron overload in both patients may be due to environmental or underlying genetic factors.

Platelet crossmatching with lymphocytotoxicity test: an effective method in alloimmunized Chinese patients.

Fifty-three patients receiving long-term platelet transfusions were regularly screened for platelet-associated antibodies by a platelet suspension immunofluorescence test (PSIFT) and a lymphocytotoxicity test (LCT). Subsequently, 24 patients became alloimmunized; all of their antibodies were of HLA specificity. Eighty-two single-donor platelet transfusions were given, and the clinical responses were considered satisfactory if the 18-hour corrected count increment was 7.5 x 10(3) per microL or higher. In the meantime, 82 pairs of patient sera and donor lymphocytes were crossmatched. Among 63 crossmatched transfusions, 53 (84%) resulted in a satisfactory increment, with a mean (+/- SEM) of 17.71 +/- 1.96 (x 10(3)/microL), and 10 did not result in a satisfactory increment. The increments after 19 unmatched transfusions and 25 random-donor (uncrossmatched) transfusions were 0.7 +/- 0.3 and 2.39 +/- 0.66, respectively. The difference was not significant (p greater than 0.05). The agreement between the LCT results and clinical response was 88 percent. Retrospectively, the corrected count increments showed no significant differences (p greater than 0.05) among three groups of HLA grading: the increments for A/BU/BX, C/D, and random HLA matches were 22.97 +/- 4.07, 15.1 +/- 1.97, and 14.85 +/- 2.04, respectively. These results suggest that platelet crossmatching by LCT is an effective method for use in alloimmunized patients, especially Chinese patients.

Comparison of stem cell viability of bone marrow cryopreserved by two different methods.

Two different cryogenic methods were used to study the preservation of murine bone marrow cells. Compared to the classical methods, in which separated mononuclear marrow cells in 10% dimethyl sulfoxide (DMSO) were cryopreserved in liquid nitrogen (-196 degrees C), a modified technique was carried out by cryopreservation of unfractionated marrow cells in a mixed protectant of 5% DMSO and 6% hydroxyethyl starch (HES) at -80 degrees C. Samples that were separately thawed after storage for 1, 4, 8, and 12 weeks were assayed for cell viability and recovery of CFU-GM and CFU-S. No macroscopic clumping of cells was noted either in fractionated or in unfractionated marrow cell cryopreservations. A mild damage, about 25% reduction of stem cells, was found at 1 week and did not deepen further. It seems that the greatest loss of stem cells occurred in the process of cryopreservation itself. Compared to prefreeze values, both a high number of cells that excluded trypan blue (87 +/- 3.4%) and a high recovery of CFU-GM (75 +/- 9.8%) and CFU-S (74 +/- 11.2) were observed in unfractionated marrow samples cryopreserved with the DMSO/HES mixture at -80 degrees C for 3 months and these results were very similar to those obtained from fractionated mononuclear marrow cells cryopreserved at -196 degrees C. The DMSO/HES protectant provides a simplified bone marrow cryopreservation technique that should be favorable to clinical application because of its high stem cell recovery and avoidance of cell-separation manipulation.

[Blood group phenotyping and their application in Taiwan].

During the 1950's and 60's as new blood group systems were identified, antigen distribution studies were performed in Europe and North America among Caucasians and American Blacks. However, to date only limited studies have been performed in Africa and Asia. Because of lack of knowledge of the antigen distribution of most other than ABO and Rho (D) blood group systems within these areas and among the people of non-Caucasian races, questions of testing needs and problems have occurred. In recent years, three big matters have been encountered off and on in blood banking in Taiwan. First, multiple-transfusion recipients develop so many alloantibodies that finding compatible donors becomes a difficult task. Second, since bone marrow transplantation technology is being instituted in many teaching hospitals, it is a task of blood banks to monitor the antigen changes of other blood group systems (including of Rh system other than D) before and after transplantation. Third, more than enough disputed paternity cases that can not be resolved by simple ABO testing. Therefore, blood banks should be staffed with suitable backgrounds to cope with the procedures needed for analysing all blood group antigens. In order to resolve all the problems effectively, we ran the tests for blood group antigens other than ABO and D in our blood bank from 1984 to 1986. A total of 31 sets of antisera were used to identify the specificity of 13 blood group system antigens of the Chinese population ranging from 99 to 2257. Based on the datum obtained, we found a significant difference between Chinese and Caucasians in the distribution of eight blood group systems (Rhesus, MNSs, Kell, Duffy, Kidd, P, Lutheran and Colton). The antigen frequency of Fya and s are 99.74, 99.91 respectively. The results are higher than those of the Caucasian population. On the other hand, Fyb and S are 9.22 and 6.56, much lower than those in Caucasians. We found no K, Lua and Cob antigens among the Chinese. We conclude that this study is a significant contribution to the knowledge of blood group antigen systems and antigen distribution, and also will benefit this population in many areas of medical care.