[Controversies and prospects for surgical treatment of pancreatic neuroendocrine neoplasms with liver metastases].

The incidence of pancreatic neuroendocrine neoplasm(pNEN) increased over the past two decades. Liver metastasis, the most common type of distal metastasis, is also one of the most important prognostic factors. Although several medical treatments, including biotherapy, chemotherapy, targeted therapy, peptide receptor radionuclide therapy and locoregional therapy, are available for pNEN with liver metastases, surgery is still the only possible treatment for cure. Currently, there are several controversies as regards surgical treatment for pNEN with liver metastases. These controversies include, but are not limited to, whether surgical resection is appropriate for pancreatic neuroendocrine tumor G3 with liver metastases, how to classify primary lesion and hepatic metastases comprehensively and accurately, what is the optimal surgical strategy for type Ⅱ liver metastases, who can benefit greatly from cytoreduction, and how to refine the Milan criteria for liver transplantation. This article aims to discuss those main controversies and provide prospects for future clinical trials.

[Frequency characteristics of horizontal semicircular canals damage and the ultrastructure analysis of crista ampullaris in patients with Meniere's disease].

Objective: To investigate the frequency characteristics and the pathological characteristics of the horizontal crista ampullaris in patients with Meniere's disease,and to analyse its structural basis. Methods: Between March, 2019 and November, 2019, seventy-two patients diagnosed as Meniere's disease (27 males and 45 females, aged from 13 to 74 years, with a course of disease ranging from 4 months to 32 years)in Shandong Provincial ENT Hospital were included.Caloric test, sinusoidal harmonic acceleration test (SHA), video-head impulse test (v-HIT), Gadolinium-enhanced inner-ear 3D-FLAIR MRI and pure tone audiometry were conducted in the patients. The function of the horizontal semicircular canal in these patients were analysed as well as its relationship with the degree of endolymphatic hydrops,clinical stage and duration. Light microscopy and transmission electron microscopy were used to observe the ultrastructure of horizontal semicircular canal crista ampullaris from six patients with refractory Meniere's disease who underwent labyrinthectomy. The number of type Ⅰ and type Ⅱ vestibular hair cells, the common pathophysiological changes of horizontal semicircular canal crista ampullaris were investigated in these patients. Statistical analysis was performed using SPSS 19.0. Results: With the increase of detection frequency, the abnormal rate decreased gradually. The abnormal rate of caloric test was 69.4% (50/72), SHA 51.4% (37/72), V-HIT 36.1% (26/72), comparation of the positive rate among the three tests showed statistically significant differences(P<0.05).Neither caloric test nor SHA had correlation with the degree of hydrops(P>0.05), but v-HIT(r=0.434,P<0.01).There was correlation with clinical stage to SHA and v-HIT(r=0.338,0.462,P<0.01), except caloric test(P>0.05).No significant relation was found with caloric test, SHA, v-HIT and course of disease(P>0.05).Morphological observation found abnormal monolayer epithelialization of the horizontal semicircular canal crista ampullaris significantly decreased number of type Ⅱ hair cells compared with type Ⅰhair cells. Hair cells showed perinuclear vacuolization, cytoplasmic vacuoles, mitochondrial electron density increasement and loss of stereocilia. Conclusions: The horizontal semicircular canal damage in the patients with Meniere's disease has a frequency-dependent characteristic, mainly occurres in low frequency area. With progress of the disease, the high frequency area of ampulla will be impaired gradually, and it is related to the degree of endolymphatic hydrops and hearing level. Hair cell injury would be observed,the frequency characteristics may be more associated with the disorder of type Ⅱ hair cells.

[Clinical pathologic analysis on 3 724 cases of salivary gland tumors].

Objective: To investigate the incidence and proportion of salivary gland tumors in order to provide new thinking for clinical diagnosis and treatment. Methods: Collected 3 724 cases salivary gland tumors diagnosed by Pathology Department of Hospital of Stomatology, Jilin University from January 1961 to December 2016. The pathological diagnosis referred to the fourth edition of head and neck-salivary gland tumor histopathological classification standard of WHO. The database was established with Microsoft Excel and analyzed with SPSS 18.0. Made a retrospective analysis and comparison on the numbers of all cases in terms of types, site, gender and age and estimate the trend with the time interval of 8 years, and then make a judgement of the trend of salivary tumors. Results: The benign tumors were more common than the malignant among all periods, the proportion of all tumors was about 2.92∶1; The top three benign tumors were polymorphous adenoma [73.78% (2 046/2 773)], Warthin tumor [15.80% (438/2 773)] and base cell adenoma [8.37% (232/2 773)]. Polymorphous adenoma took up 54.94% (2 046/3 724) of all tumors. The top three malignant tumors were mucous epidermoid carcinoma [31.44% (299/951)], adenoid cystic carcinoma [26.92% (256/951)] and adenocarcinoma [11.88% (113/951)]. As for sex, male female ratio was 0.83∶1. As for site, the pathogenic site of tumors was mainly in parotid gland [63.75% (2 374/3 724)], followed by palatal gland [16.50% (615/3 724)], then submandibular gland [12.67% (472/3 724)]; As for age, the common age was between 51 and 60 years old [23.74% (884/3 724)], followed by 41 to 50 years old [21.56%(803/3 724)]. Conclusions: The incidence of benign and malignant salivary gland tumor increased in the 56 years. Females showed a higher incidence. The majority tumors occurred in parotid gland. The most common salivary gland tumor was pleomorphic adenoma and the most common malignant tumor was mucous epidermoid carcinoma. The most common age was in 51-60 years old period.

[A retrospective clinical study of 3 382 cases of malignant oral maxillofacial tumors].

To investigate the incidence of malignant tumors in oral and maxillofacial region and the pathological features of various tumors, a total of 3 382 cases of malignant tumors in oral and maxillofacial region admitted to Jilin University from Januarary 2000 to December 2017. The characteristics of age, sex, location and pathological types of all kinds of tumors were analyzed. The median onset age is 57 years old, 51 to 70 years old is a high-risk age group, the ratio of male to female was 1.9∶1. The primary tumor location is tongue, gingiva and floor of mouth. Epithelial, lymphatic hematopoietic system, bone and soft tissue were the three major sources of tumor tissue, and squamous cell carcinoma was the most common pathological type (65.1%), followed by mucoepidermoid carcinoma and adenoid cystic carcinoma. In summary, oral and maxillofacial malignancies have a high incidence in elderly men, and tongue is the most common site of disease. Epithelial-origin and squamous cell carcinomas are the first of their origins and pathological types, respectively.

Intensity-modulated radiotherapy increases dose to the brachial plexus compared with conventional radiotherapy for head and neck cancer.

OBJECTIVE: The preferential use of intensity-modulated radiotherapy (IMRT) over conventional radiotherapy (CRT) in the treatment of head and neck cancer has raised concerns regarding dose to non-target tissue. The purpose of this study was to compare dose-volume characteristics with the brachial plexus between treatment plans generated by IMRT and CRT using several common treatment scenarios. METHOD: The brachial plexus was delineated on radiation treatment planning CT scans from 10 patients undergoing IMRT for locally advanced head and neck cancer using a Radiation Therapy Oncology Group-endorsed atlas. No brachial plexus constraint was used. For each patient, a conventional three-field shrinking-field plan was generated and the dose-volume histogram (DVH) for the brachial plexus was compared with that of the IMRT plan. RESULTS: The mean irradiated volumes of the brachial plexus using the IMRT vs the CRT plan, respectively, were as follows: V50 (18±5 ml) vs (11±6 ml), p = 0.01; V60 (6±4 ml) vs (3±3 ml), p = 0.02; V66 (3±1 ml) vs (1±1 ml), p = 0.04, V70 (0±1 ml) vs (0±1 ml), p = 0.68. The maximum point dose to the brachial plexus was 68.9 Gy (range 62.3-78.7 Gy) and 66.1 Gy (range 60.2-75.6 Gy) for the IMRT and CRT plans, respectively (p = 0.01). CONCLUSION: Dose to the brachial plexus is significantly increased among patients undergoing IMRT compared with CRT for head and neck cancer. Preliminary studies on brachial plexus-sparing IMRT are in progress.

Reversible twinning in pure aluminum.

Twinning in metals is normally a permanent plastic deformation mechanism. Here we report reversible twinning in high stacking fault energy (SFE) aluminum. Twinning and spontaneous detwinning at the crack tip have been captured in situ during tensile straining under a transmission electron microscope. Both the in situ observation and the molecular dynamics simulations reveal a two-stage detwinning process. The high propensity for detwinning is due to the high SFE and the low frictional forces against the detwinning partial dislocations in Al. This discovery of reversible twinning has implications for the deformation of other high SFE materials.

Integrated modeling of microwave food processing and comparison with experimental measurements.

This paper presents an integrated electromagnetic and thermal model for the microwave processing offood packages. The model is developed by combining the edge finite element formulation of the 3-D vector electromagnetic field in the frequency domain and the node finite element solution of the thermal conduction equation. Both mutual and one-way coupling solution algorithms are discussed. Mutual coupling entails the iterative solution of the electromagnetic field and the thermal field, because the physical properties are temperature-dependent. The one-way coupling is applicable when the properties are temperature independent or this dependence is weak. Mesh sensitivity and shape regularity for the edge element based formulation for computational electromagnetics are discussed in light of available analytical solutions for a simple wave guide. The integrated model has been used to study the electromagnetic and thermal phenomena in a pilot scale microwave applicator with and without the food package immersed in water. The calculated results are compared with the experimentally measured data for the thermal fields generated by the microwave heating occurring in a whey protein gel package, and reasonably good agreement between the two is obtained.

The flavonoid baicalin inhibits superantigen-induced inflammatory cytokines and chemokines.

Excessive release of proinflammatory cytokines mediates the toxic effect of superantigenic staphylococcal exotoxins (SE). Baicalin, a flavone isolated from the Chinese herb Scutellaria baicalensis Georgi and used in China to treat infectious diseases, inhibited SE-stimulated T-cell proliferation (by 98%) and production of interleukin 1beta, interleukin 6, tumor necrosis factor, interferon gamma, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta mRNA and protein by human peripheral blood mononuclear cells. These data suggest that baicalin may be therapeutically useful for mitigating the pathogenic effects of SE by inhibiting the signaling pathways activated by superantigens.

The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1.

The G protein-coupled 7 transmembrane (STM) chemoattractant receptors can be inactivated by heterologous desensitization. Earlier work showed that formly peptide receptor-like 1 (FPRL1), an STM receptor with low affinity for the bacterial chemotactic peptide formyl-methionyl-leucyl-phenylalamine (fMLF), is activated by peptide domains derived from the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp120 and its activation results in desensitization and down-regulation of the chemokine receptors CCR5 and CXCR4 from monocyte surfaces. This study investigated the possibility of interfering with the function of CCR5 or CXCR4 as HIV-1 coreceptors by activating FPRL1. Cell lines were established expressing FPRL1 in combination with CD4/CXCR4 or CD4/CCR5 and the effect of a synthetic peptide, WKYMVm, a potent activator of formyl peptide receptors with preference for FPRL1 was determined. Both CXCR4 and CCR5 were desensitized by activation of the cells with WKYMVm via a staurosporine-sensitive pathway. This desensitization of CXCR4 and CCR5 also attenuated their capacity as the fusion cofactors for HIV-1 envelope glycoprotein and resulted in a significant inhibition of p24 production by cell lines infected with HIV-1 that use CCR5 or CXCR4 as coreceptors. Furthermore, WKYMVm inhibited the infection of human peripheral monocyte-derived macrophages and CD4(+) T lymphocytes by R5 or X4 strains of HIV-1, respectively. These results indicate that heterologous desensitization of CCR5 and CXCR4 by an FPRL1 agonist attenuates their major biologic functions and suggest an approach to the development of additional anti-HIV-1 agents. (Blood. 2001;97:2941-2947)

Flavonoid baicalin inhibits HIV-1 infection at the level of viral entry.

Baicalin (BA) is a flavonoid compound purified from medicinal plant Scutellaria baicalensis Georgi and has been shown to possess anti-inflammatory and anti-HIV-1 activities. In an effort to elucidate the mechanism of the anti-inflammatory effect of BA, we recently found that this flavonoid compound was able to form complexes with selected chemokines and attenuated their capacity to bind and activate receptors on the cell surface. These observations prompted us to investigate whether BA could inhibit HIV-1 infection by interfering with viral entry, a process known to involve interaction between HIV-1 envelope proteins and the cellular CD4 and chemokine receptors. We found that BA at the noncytotoxic concentrations, inhibited both T cell tropic (X4) and monocyte tropic (R5) HIV-1 Env protein mediated fusion with cells expressing CD4/CXCR4 or CD4/CCR5. Furthermore, presence of BA at the initial stage of HIV-1 viral adsorption blocked the replication of HIV-1 early strong stop DNA in cells. Since BA did not inhibit binding of HIV-1 gp120 to CD4, we propose that BA may interfere with the interaction of HIV-1 Env with chemokine coreceptors and block HIV-1 entry of target cells. Therefore, BA can be used as a basis for developing novel anti-HIV-1 agents.

Isoform-specific insertion near the Grb2-binding domain modulates the intrinsic guanine nucleotide exchange activity of hSos1.

Two human hSos1 isoforms (Isf I and Isf II; Rojas et al., Oncogene 12, 2291-2300, 1996) defined by the presence of a distinct 15 amino acid stretch in one of them, were compared biologically and biochemically using representative NIH3T3 transfectants overexpressing either one. We showed that hSos1-Isf II is significantly more effective than hSos1-Isf I to induce proliferation or malignant transformation of rodent fibroblasts when transfected alone or in conjunction with normal H-Ras (Gly12). The hSos1-Isf II-Ras cotransfectants consistently exhibited higher saturation density, lower cell-doubling times, increased focus-forming activity and higher ability to grow on semisolid medium and at low serum concentration than their hSos1-Isf I-Ras counterparts. Furthermore, the ratio of GTP/GDP bound to cellular p21ras was consistently higher in the hSos1-Isf II-transfected clones, both under basal and stimulated conditions. However, no significant differences were detected in vivo between Isf I- and Isf II-transfected clones regarding the amount, stability and subcellular localization of Sos1-Grb2 complex, or the level of hSos1 phosphorylation upon cellular stimulation. Interestingly, direct Ras guanine nucleotide exchange activity assays in cellular lysates showed that Isf II transfectants consistently exhibited about threefold higher activity than Isf I transfectants under basal, unstimulated conditions. Microinjection into Xenopus oocytes of purified peptides corresponding to the C-terminal region of both isoforms (encompassing the 15 amino acid insertion area and the first Grb2-binding motif) showed that only the Isf II peptide, but not its corresponding Isf I peptide, was able to induce measurable rates of meiotic maturation, and synergyzed with insulin, but not progesterone, in induction of GVBD. Our results suggest that the increased biological potency displayed by hSos1-Isf II is due to higher intrinsic guanine nucleotide exchange activity conferred upon this isoform by the 15 a.a. insertion located in proximity to its Grb2 binding region.

Clinical and experimental study on therapeutic effect of Weixibaonizhuanwan on gastric precancerous lesions.

AIM: To study the therapeutic effect of Weixibaonizhuanwan on gastric precancerous lesions. METHODS: Thirty-six patients with gastric precancerous lesions were treated with Weixibaonizhuanwan for 3 mo. Thirteen (36.1%) patients presented with mild atrophic gastritis, 14 (38.9%) with moderate atrophic gastritis, and nine (25.0%) with severe atrophic gastritis. Twenty-two (61.1%) and 27 (75.0%) of the cases were accompanied by intestinal metaplasia (IM) and dysplasia (DYS), respectively. Twenty of the 36 patients were men and 16 were women, ranging from 30 to 67 years in age, with 61.1% of the patients being 40-59 years old. The duration of the disease in these patients ranged from 3 mo to 21 years, with 20 (55.6%) patients experiencing durations of the disease between 5 and 10 years. The clinical manifestations of the disease in these patients included fullness of the abdomen (31 cases), abdominalgia (27 cases), anorexia (30 cases), eructation (26 cases), pantothenic acid (6 cases), and loose stool (9 cases). Patients were treated with Weixibaonizhuanwan and symptom improvement, level of atrophy of the gastric mucosa, and IM and DYS progression were analyzed. RESULTS: After a 3-mo treatment with Weixibaonizhuanwan, seven patients experienced recovery. The treatment was effective in 11 cases, improved symptoms in 13 cases, and was ineffective in five cases. The overall efficacy rate was 86.1%. In patients with mild atrophic gastritis (n = 13), 11 improved into superficial gastritis and two experienced no improvement. In 14 cases of moderate gastritis, four cases improved into superficial gastritis and seven turned into mild atrophic gastritis, with three patients experiencing no improvement. Among severe atrophic gastritis patients (n = 9), five improved into moderate atrophic gastritis after treatment and four experienced no improvement. The overall efficacy rate in chronic atrophic gastritis patients was 77.8%. Among 9 patients with IM, IM disappeared in six cases, whereas three cases showed no improvement after treatment. In cases with moderate IM (n = 10), IM disappeared in two, turned into mild IM in five, and showed no change in three. Out of four cases with IM, one case turned into moderate IM and three showed no change. The overall efficacy rate in IM patients was 63.6%. Out of 16 cases of mild DYS, DYS disappeared in 11, whereas five cases showed no change. Out of nine cases of moderate DYS, DYS disappeared in two and turned into mild DYS in five cases, with two patients experiencing no change after treatment. No improvement was observed in the two cases of severe DYS after treatment. The overall efficacy rate in DYS patients was 66.7%. After treatment, expression of carcinoembryonic antigen (CEA) and proliferating cell nuclear antigen (PCNA) in gastric mucosa significantly decreased (P < 0.01). Before treatment, cancer staging of these patients by positive CEA expression was I, II, III, and IV in 13, 12, 9, and 2 cases, respectively. After treatment, the number of cases per stage changed to 25, 7, 3, and 1, respectively. Similarly, before treatment, staging by positivity of PCNA expression was I, II, III, and IV in 16, 11, 10, and 4 cases, respectively, and changed to 21, 9, 5, and 1, respectively, after treatment. CONCLUSION: The use of Weixibaonizhuanwan in the treatment of gastric precancerous lesions showed promising therapeutic effects in patients after 3-mo treatments.

Macrophage-stimulating protein activates Ras by both activation and translocation of SOS nucleotide exchange factor.

Macrophage-stimulating protein (MSP) is a chemotactic factor that activates the receptor tyrosine kinase RON. The involvement of Ras in MSP-induced signal transduction was investigated. Here we demonstrate that, in RON-transfected MDCK cells, an active GTP-bound form of Ras was rapidly accumulated by MSP treatment and the Ras-guanine nucleotide exchange activity in SOS immunoprecipitates was concomitantly increased. GAP activity was not changed under the same conditions used. Furthermore, the SH2 domain of adaptor protein GRB2, but not Shc, associated with the activated RON-beta chain, and GRB2-SOS complexes translocated from the cytosol to the membrane upon MSP treatment. These results strongly suggest that MSP activates Ras through RON, and that MSP-induced activation of Ras might be controlled by both the enhancement of catalytic exchange activity of SOS and its translocation to the membrane where its target Ras is localized.

Mitogenic activation of the Ras guanine nucleotide exchange factor in NIH 3T3 cells involves protein tyrosine phosphorylation.

We report biochemical evidence that epidermal growth factor and platelet-derived growth factor stimulate the Ras guanine nucleotide exchange factor activity in quiescent NIH 3T3 cells. Moreover, the exchange activity is constitutively enhanced in NIH 3T3 cells transformed by Src and ErbB2 oncogenic tyrosine protein kinases (TPKs), whereas transformation by oncogenic Mos and Raf does not alter the activity. GTPase-activating protein activity was not affected under these conditions. Overexpression of pp60c-Src mutants containing activated and suppressor TPK mutations resulted in stimulation and inhibition of the exchange factor activity, respectively. A TPK inhibitor, genistein, prevented the activation of the exchange factor in epidermal growth factor/platelet-derived growth factor-treated cells and src-transformed cells. Furthermore, the exchange factor activity bound to an anti-phosphotyrosine antibody immunoaffinity column. These findings suggest that the guanine nucleotide exchange factor, but not GTPase-activating protein, plays a major role in the Ras activation in cell proliferation initiated by growth factor receptor TPKs and malignant transformation by oncogenic TPKs and that tyrosine phosphorylation of either the exchange factor or a tightly bound protein(s) may mediate the activation of the exchange factor by these TPKs.

Nerve growth factor stimulation of the Ras-guanine nucleotide exchange factor and GAP activities.

The biological activity of Ras proteins is thought to be controlled by the guanine nucleotide exchange factor and the guanosine triphosphatase activating protein (GAP). Treatment of rat pheochromocytoma PC-12 cells with nerve growth factor (NGF) increased the amount of active Ras guanosine triphosphate complex and stimulated the activities of both the guanine nucleotide exchange factor and GAP. In PC-12 cells that overexpressed the tyrosine kinase encoded by the trk proto-oncogene (a component of the high-affinity NGF receptor), the NGF-induced activation of the regulatory proteins was potentiated. These results suggest that the NGF receptor system enhances the activities of both the guanine nucleotide exchange factor and GAP and that the activation of Ras might be controlled by the balance in activity between these two regulatory proteins.

Decrease in cytokine production by HIV-infected macrophages in response to LPS-mediated activation.

The capacity of human monocytes/macrophages (M/M) infected with a human immunodeficiency virus-1 (HIV-1) isolate to produce several immunomodulating cytokines including interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and macrophage chemoattractant and activating factor (MCAF) was examined. Although HIV infection itself induced significant increases in the level of mRNAs for IL-1 beta, TNF-alpha, IL-6, and IL-8, the levels of lipopolysaccharide (LPS)-induced mRNAs for IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, IL-8, and MCAF were decreased over those of uninfected LPS-stimulated cells. In addition, HIV-infected M/M produced lower amounts of IL-8 protein, as measured by radioimmunoassay over an 18-day culture period. These results suggest that HIV infection generally suppresses the LPS-inducible cytokine production in human M/M. The impact of the role of these cytokines in the immunity and pathogenesis of HIV-1 infection is discussed.

A new class of anti-HIV agents: GAP31, DAPs 30 and 32.

Three inhibitors of human immunodeficiency virus (HIV) have been isolated and purified to homogeneity from Euphorbiaceae himalaya seeds (Gelonium multiflorum) and carnation leaves (Dianthus caryophyllus). These proteins, GAP 31 (Gelonium Anti-HIV Protein 31 kDa) and DAPs 30 and 32 (dianthus anti-HIV proteins, 30 and 32 kDa), inhibit HIV-1 infection and replication in a dose-dependent manner with little toxicity to target cells. The therapeutic indices of these compounds are in the order 10(4), suggesting that they may be clinically important agents in the treatment of AIDS. The N-terminal amino acid sequences of these proteins show little homology to those of previously described anti-HIV proteins. The structure-function features of these HIV inhibitors, based on the 40-60 amino acid residues of N-terminal sequences, are examined.

TAP 29: an anti-human immunodeficiency virus protein from Trichosanthes kirilowii that is nontoxic to intact cells.

An anti-human immunodeficiency virus (anti-HIV) protein capable of inhibiting HIV-1 infection and replication has been isolated and purified to homogeneity from Trichosanthes kirilowii. This protein, TAP 29 (Trichosanthes anti-HIV protein, 29 kDa), is distinct from trichosanthin [also known as GLQ 223 (26 kDa)] in size, N-terminal amino acid sequence, and cytotoxicity. In addition to three conservative substitutions--namely, Arg-29 to Lys, Ile-37 to Val, and Pro-42 to Ser--a total difference of residues 12-16 was found. TAP 29 yielded -Lys-Lys-Lys-Val-Tyr-, whereas trichosanthin has -Ser-Ser-Tyr-Gly-Val-. Although the two proteins exhibit similar anti-HIV activity, as measured by syncytium formation, p24 expression, and HIV reverse transcriptase activity, they differ significantly in cytotoxicity, as measured by their effects on cellular DNA and protein syntheses. At the dose level of the bioassays, 0.34-340 nM, trichosanthin demonstrates a dose-dependent toxic effect on host cells. TAP 29 displays no toxic effect, even at 100 X ID50, whereas trichosanthin demonstrates 38% and 44% inhibition on cellular DNA and protein synthesis, respectively. These results indicate that the therapeutic index of TAP 29 is at least two orders of magnitude higher than that of trichosanthin. Thus TAP 29 may offer a broader safe dose range in the treatment of AIDS.