[Clinical characteristics of 42 patients with different subspecies of Mycobacterium abscessus complex pulmonary disease].

Objective: To compare clinical features and treatment outcomes of Mycobacterium abscessus (M.abscessus) and Mycobacterium massiliense (M.massiliense) pulmonary disease. Methods: A retrospective analysis was performed for 42 patients diagnosed with M.abscessus complex pulmonary disease for the first time in Guangzhou Chest Hospital from January to September 2021. The age of the 42 patients was 17-73 years, including 15 males and 27 females. According to the targeted next-generation sequencing, the patients were divided into M.abscessus group (28 patients, including 10 males and 18 females) and M. massiliense group (14 patients, including 5 males and 9 females). The clinical characteristics, radiological findings, drug sensitivity and clinical efficacy evaluation at 6 months of the two groups were compared. χ2 test and t-test were used for comparison between two groups. Results: The main symptoms in M. abscessus and M. massiliense groups were cough and sputum production. Radiological findings were significantly more frequent in the M. abscessus group than in the M. massiliense group, tree-in-bud sign [22/28 (78.5%) vs. 5/14], nodular bronchiectasis [27/28 (96.4%) vs. 11/14], and lesions involving more than three lung fields [23/28 (82.1%) vs. 7/14]. Both groups showed high levels of resistance to all antimicrobials. The sensitivity rate of the M. massiliense group to clarithromycin was higher than that of the M. abscessus[13/14 vs. 15/28 (53.5%)], and the success rate of treatment was significantly higher in patients with M. massiliense at the 6-month efficacy evaluation. Conclusions: The radiological findings, drug sensitivity and treatment outcomes differ between M. abscessus and M. massiliense pulmonary disease. Improving the identification of bacterial subspecies in clinical practice can effectively improve the diagnosis and treatment.

The effect of loneliness on depression in young people: a multiple mediated effects model.

OBJECTIVE: The COVID-19 pandemic led to prolonged isolation and disrupted people's social relationships, contributing to increased loneliness among students. Loneliness is associated with various psychological disorders, including depression, which may result in severe consequences such as self-harm and suicide. This study aims to investigate the factors through which loneliness influences depression. SUBJECTS AND METHODS: The study involved administering questionnaires to 879 secondary and higher education students in Guangzhou, Guangdong Province, China, during the COVID-19 epidemic. The data that were gathered underwent a comprehensive analysis. RESULTS: The data analysis revealed a significant positive predictive effect of loneliness on depression. Additionally, the study found that a goal-oriented approach and resilience partially mediated the relationship between feelings of loneliness and symptoms of depression. Furthermore, resilience and goal focus were identified as mediators in a chain, independent of the levels of expression inhibition and cognitive reappraisal. Cognitive reappraisal showed a negative moderating effect on the mediation between loneliness and depression. Moreover, expressive inhibition positively mediated the relationship between loneliness and depression, with resilience playing a role in this association. CONCLUSIONS: The findings indicate that the inability to alleviate negative emotions through socialization and interpersonal companionship during COVID-19 contributed to increased loneliness and subsequent depression. Reduced resilience due to loneliness may lead individuals to project unfavorable interpersonal experiences onto other aspects of life and believe they are incapable of overcoming challenges, thereby deteriorating depression conditions. Enhancing an individual's resilience may help them better adapt to the pandemic-induced changes, mitigating the risk of depression. Similarly, individuals with high levels of goal focus tend to learn from their experiences, adjust their pace of life, and exhibit lower levels of depression. Targeted interventions to enhance goal focus may be beneficial in reducing depression levels. Moreover, individuals who inhibit the expression of their unhappiness may experience elevated depression levels, while those with high cognitive reappraisal skills tend to experience less depression by altering their cognitive perspective on distressing situations.

Botrytis polygoni, a new species of the genus Botrytis infecting Polygonaceae in Gansu, China.

A new species, Botrytis polygoni, was isolated from several species of Polygonaceae in 2011 and 2012 in Tongwei County, Gansu Province, China. The species infects Fagopyrum esculentum, F. tataricum, and Fallopia convolvulus, causing brown leaf spots and large blotches with concentric rings in the field. Botrytis polygoni is morphologically characterized by conidia spherical, unicellular, hyaline to pale brown or brown, (10.2-)14.3-21.4(-23.5) µm; and sclerotia black, spherical to subspherical, allantoid, or irregular-shaped, 0.2-4.1 × 0.1-3.0 mm. Comparison of the nuc rDNA internal transcribed spacer region (ITS1-5.8S-ITS2) sequences confirmed its placement in the genus Botrytis. Phylogenetic analysis based on the protein-coding genes glyceraldehyde 3-phosphate dehydrogenase (G3PDH), heat shock protein 60 (HSP60), and DNA-dependent RNA polymerase subunit II (RPB2) showed that the new species is clustered close but separate from Botrytis pyriformis, which was distant from 37 other Botrytis species and 17 undescribed species. Pathogenicity tests showed that the new species has aggressive pathogenicity to four species of Polygonaceae, specifically Fag. tataricum, Fal. convolvulus, Polygonum sibiricum, and Pol. aviculare, weak pathogenicity to Vicia faba in the Fabaceae, and no pathogenicity to eight other tested plants: Amaranthus retroflexus, Cirsium arvense, Convolvulus arvensis, Kalanchoe blossfeldiana, Lagopsis supine, Mentha canadensis, Plantago asiatica, and Raphanus sativus.

Clinical features and treatment outcomes of eosinophilic gastroenteritis : an analysis of 28 cases.

BACKGROUND: Eosinophilic gastroenteritis (EG) is uncommon disease, and the pathogenesis of this disease have yet to be fully clarified. AIM: This study was to describe the clinical manifestations, endoscopic features and treatment outcomes of a cohort of patients with EG. METHOD: This retrospective study was included 28 consecutive patients who were diagnosed EG between January 2011 and December 2015 in Taizhou Hospital. The patients' clinical manifestations, endoscopic features and treatment outcomes were reviewed from a prospectively maintained database. RESULTS: Twenty-eight patients with EG were enrolled in the study (median age 54 years). The main symptoms were abdominal pain (78.6%), abdominal distension (50.0%), nausea and vomiting (28.6%) and diarrhea (25.0%). Laboratory examinations showed the elevation of blood eosinophil count (85.7%), serum IgE (71.4%). Endoscopic findings included small patchy mucosal erythema or erosions (75.0%), mucosal fold thickening (17.9%), submucosal nodules (21.4%), small gastroduodenal ulcers (14.3%). Twenty patients were treated and responded to prednisolone but five patients (25.0%) relapsed during the follow-up. The other 8 patients were treated with loratadine, proton pump inhibitors and dietary modification, 5 patients had clinical resolution during the follow-up. The other 3 patients did not achieve clinical remission, and then were given prednisone treatment. CONCLUSION: For some patients with gastrointestinal symptoms and peripheral eosinophilia, a high suspicion of EG is necessary and multiple endoscopic examinations might be helpful in diagnosis of EG. Most patients with EG could achieve remission after with the treatment of steroid or dietary elimination therapy.

[Copy number aberrations of genes related to extrohepatic metastasis-free survival after operation for hepatocellular carcinoma].

Objective: To investigate the molecular markers of copy number aberrations (CNAs) of genes related to extrohepatic metastasis-free survival after the operation for hepatocellular carcinoma (HCC). Methods: The CNA status of 20 candidate genes in 66 HCC samples was detected by microarray comparative genomic hybridization. The associations between gene CNAs and extrohepatic metastasis-free survival were evaluated using the Cox regression model, Log-rank test, and Kaplan-Meier survival analysis. Results: Multivariate Cox analysis revealed that the independent risk factors for metastasis-free survival were MDM4 gain (hazard ratio [HR] = 2.74, 95% confidence interval [CI] = 1.18-6.37, P < 0.05), APC loss (HR = 8.43, 95% CI = 2.48-28.66, P < 0.01), and BCL2L1 gain (HR = 3.45, 95% CI = 1.13-10.52, P < 0.05) and the independent protective factor was FBXW7 loss (HR = 0.32, 95% CI = 0.12-0.89, P < 0.05). By stepwise Cox regression analysis, three CNAs related to metastasis-free survival were screened out: MDM4 gain (HR = 2.71, 95% CI = 1.11-6.64, P < 0.05), APC loss (HR = 7.19, 95% CI = 1.88-27.60, P < 0.005), and FBXW7 loss (HR = 0.16, 95% CI = 0.05-0.46, P < 0.01). There were significant differences in metastasis-free survival rate between the HCC patients with FBXW7 loss and without MDM4 gain or APC loss, those with MDM4 gain and/or APC loss and without FBXW7 loss, and those with other CNA combinations (log-rank test, P < 0.01). Conclusion: MDM4 gain, APC loss, and FBXW7 loss are the independent prognostic factors for extrohepatic metastasis-free survival after the operation for HCC and can be used to predict the risk of extrohepatic metastasis after the operation for HCC.

[Prenatal diagnosis of Thailand deletion of α-thalassemia 1 families].

OBJECTIVE: To conduct analysis and prenatal diagnosis on 11 couples carrying Thailand deletion (--(THΑI)) α-thalassemia 1, so as to provide information for clinical genetic counseling on α-thalassemia 1. METHODS: Altogether 11 Thailand deletion (--(THΑI)) α-thalassemia 1 families were collected from Fujian Maternal and Children Health Hospital from May 2009 to September 2015. Gap-polymerase chain reaction (gap-PCR) and reverse dot blot (RDB) technology were used to detect the thalassemia mutations in the couples and fetuses. RESULTS: In one family, Thailand deletion α-thalassemia 1 was detected in both the pregnant woman and her husband. In 10 families, Thailand deletion α-thalassemia 1 was detected in either the pregnant women or the husband, while the spouses had α-thalassemia heterozygote (1 combined with ß thalassemia heterozygote). Thailand deletion α-thalassemia 1 family members all had lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). In prenatal diagnosis of the 12 fetuses, 4 fetuses were found with hemoglobin(Hb) Bart's hydrops fetalis syndrome, 5 were with α-thalassemia heterozygote, and 3 were normal. CONCLUSIONS: For couples with positive hematological phenotype but normal results in routine genetic examination of α-thalassemia, attention should be paid especially for with a history of having babies of hydrops fetalis syndrome or hemoglobin H disease. It is necessary to consider the possibility of the rare Thailand deletion (--(THΑI)) α-thalassemia 1. Prenatal diagnosis for high-risk families plays an important role.

The inhibition of high-voltage-activated calcium current by activation of MrgC11 involves phospholipase C-dependent mechanisms.

High-voltage-activated (HVA) calcium channels play an important role in synaptic transmission. Activation of Mas-related G-protein-coupled receptor subtype C (MrgC; mouse MrgC11, rat homolog rMrgC) inhibits HVA calcium current (ICa) in small-diameter dorsal root ganglion (DRG) neurons, but the intracellular signaling cascade underlying MrgC agonist-induced inhibition of HVA ICa in native DRG neurons remains unclear. To address this question, we conducted patch-clamp recordings in MrgA3-eGFP-wild-type mice, in which most MrgA3-eGFP(+) DRG neurons co-express MrgC11 and can be identified for recording. We found that the inhibition of HVA ICa by JHU58 (0.001-100nM, a dipeptide, MrgC-selective agonist) was significantly reduced by pretreatment with a phospholipase C (PLC) inhibitor (U73122, 1µM), but not by its inactive analog (U73343) or vehicle. Further, in rats that had undergone spinal nerve injury, pretreatment with intrathecal U73122 nearly abolished the inhibition of mechanical hypersensitivity by intrathecal JHU58. The inhibition of HVA ICa in MrgA3-eGFP(+) neurons by JHU58 (100nM) was partially reduced by pretreatment with a Gßγ blocker (gallein, 100µM). However, applying a depolarizing prepulse and blocking the Gαi and Gαs pathways with pertussis toxin (PTX) (0.5µg/mL) and cholera toxin (CTX) (0.5µg/mL), respectively, had no effect. These findings suggest that activation of MrgC11 may inhibit HVA ICa in mouse DRG neurons through a voltage-independent mechanism that involves activation of the PLC, but not Gαi or Gαs, pathway.

Comparison of intensity-dependent inhibition of spinal wide-dynamic range neurons by dorsal column and peripheral nerve stimulation in a rat model of neuropathic pain.

BACKGROUND: Spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) are thought to reduce pain by activating a sufficient number of large myelinated (Aß) fibres, which in turn initiate spinal segmental mechanisms of analgesia. However, the volume of neuronal activity and how this activity is associated with different treatment targets is unclear under neuropathic pain conditions. METHODS: We sought to delineate the intensity-dependent mechanisms of SCS and PNS analgesia by in vivo extracellular recordings from spinal wide-dynamic range neurons in nerve-injured rats. To mimic therapeutic SCS and PNS, we used bipolar needle electrodes and platinum hook electrodes to stimulate the dorsal column and the tibial nerve, respectively. Compound action potentials were recorded to calibrate the amplitude of conditioning stimulation required to activate A-fibres and thus titrate the volume of activation. RESULTS: Dorsal column stimulation (50 Hz, five intensities) inhibited the windup (a short form of neuronal sensitization) and the C-component response of wide-dynamic range neurons to graded intracutaneous electrical stimuli in an intensity-dependent manner. Tibial nerve stimulation (50 Hz, three intensities) also suppressed the windup in an intensity-dependent fashion but did not affect the acute C-component response. CONCLUSIONS: SCS and PNS may offer similar inhibition of short-term neuronal sensitization. However, only SCS attenuates spinal transmission of acute noxious inputs under neuropathic pain conditions. Our findings begin to differentiate peripheral from spinal-targeted neuromodulation therapies and may help to select the best stimulation target and optimum therapeutic intensity for pain treatment.

Temporal changes in MrgC expression after spinal nerve injury.

Mas-related G-protein-coupled receptor subtype C (MrgC) may play an important role in pain sensation. However, the distribution of MrgC receptors in different subpopulations of rodent dorsal root ganglion (DRG) neurons has not been clearly demonstrated owing to a lack of MrgC-selective antibody. It is also unclear whether peripheral nerve injury induces different time-dependent changes in MrgC expression in injured and uninjured DRG neurons. Here we showed that MrgC immunoreactivity is distributed in both IB4-positive (non-peptidergic) and calcitonin gene-related peptide-positive (peptidergic) DRG neurons in mice and rats. Importantly, the MrgC mRNA level and MrgC immunoreactivity were both decreased in the injured L5 DRG compared to corresponding levels in the contralateral (uninjured) DRG in rats on days 14 and 30 after an L5 spinal nerve ligation. In contrast, mRNA and protein levels of MrgC were increased in the adjacent uninjured L4 DRG. Thus, nerve injury may induce temporal changes in MrgC expression that differ between injured and uninjured DRG neurons. In animal behavior tests, chronic constriction injury of the sciatic nerve induced mechanical pain hypersensitivity in wild-type mice and Mrg-clusterΔ(-/-) mice (Mrg KO). However, the duration of mechanical hypersensitivity was longer in the Mrg KO mice than in their wild-type littermates, indicating that activation of Mrgs may constitute an endogenous mechanism that inhibits the maintenance of neuropathic pain in mice. These findings extend our knowledge about the distribution of MrgC in rodent DRG neurons and the regulation of its expression by nerve injury.

In vitro radiosensitization of human cervical carcinoma cells by combined use of 13-cis-retinoic acid and interferon-alpha2a.

BACKGROUND: Significant antitumor activity has been reported with the combined use of 13-cis-retinoic acid (cRA) and interferon-alpha2a (IFN-alpha) in the treatment of advanced-stage cervical cancers and skin cancers. Since IFN-alpha has been shown to be a modest radiation enhancer for selected malignant tumor cells and the cytotoxic activity is more enhanced by combining cRA and IFN-alpha, we hypothesized that the exposure of selected human carcinoma cells to combined cRA and IFN-alpha would render the cells highly radiosensitive. METHODS AND MATERIALS: Two human cervical carcinoma cell lines, ME-180 and HeLa-S3, were chosen for the present study because of the different characteristics of the retinoic acid receptor status of the cell lines. To demonstrate the effects of combined cRA and IFN-alpha treatment on radiation response, we exposed the cells to cRA, IFN-alpha, or a combination of the drugs for 72 h before radiation. Experiments were carried out at minimally cytotoxic concentrations of the drug for radiation studies. End points of the study were cell growth inhibition and clonogenic ability of the single-plated cells. Effects of cRA and IFN-alpha on radiation response were quantitatively analyzed by constructing the radiation cell survival curves of ME-180 and HeLa cells. RESULTS: ME-180 cells exhibited varying degrees of cytotoxicity with cRA and IFN-alpha, while HeLa cells showed no toxic effects with the same treatment. Combined treatment of cRA and IFN-alpha produced an additive cytotoxic effect in ME-180 cells. Radiosensitization was minimal when ME-180 cells were treated with either cRA or IFN-alpha before radiation. When ME-180 cells were exposed to 10 microM cRA for 48 h and 1000 U/ml IFN-alpha for 24 h prior to radiation, there was a significant enhancement in radiation-induced cell killing; the dose modification factor was 2.1 +/- 0.9 at the 1% cell-survival level. On the other hand, HeLa-S3 cells exhibited no increased cytotoxicity or radiation enhancement under the same experimental conditions. CONCLUSION: The present data provide a radiobiological basis for using cRA and IFN-alpha as a combination radiosensitizer in selected human carcinoma cells.

Hyperfractionated accelerated radiation therapy for non-small cell lung cancer: clinical phase I/II trial.

PURPOSE: In an attempt to improve local control and survival of nonsmall cell lung cancer (NSCLC), hyperfractionated accelerated radiation therapy (HART) was carried out as a clinical phase I/II trial. METHODS AND MATERIALS: HART was delivered by 1.1 Gy/fraction, three fractions per day with intervals of 4 h and five treatment days per week. The clinical tumors were irradiated to 74.3 Gy (72.6-75.9)/66-69 fx, 33 days (29-40) (not corrected for lung density), and the subclinical lesions, to 50.0 Gy (48.4-50.6)/44-46 fx, 33 days (29-40). Sixty-nine patients with NSCLC were enrolled in this study. Nine patients were withdrawn from the study during HART due to different reasons. Sixty patients formed the study for outcome analyses. They were 57 males and 3 females with median age of 61 years (21-77). There were 41 cases of squamous cell carcinoma, 15 cases of adenocarcinoma, and 4 cases of large cell carcinoma. Overall, favorable patients (KPS > or = 70, weight loss < 5% and Stages I, II, IIIa) accounted for 73% (44 of 60) of all patients. Forty-four patients (73%) received adjuvant chemotherapy (DDP + VP16) with median cycles of 1.8 before and/or after HART. In order to compare the outcome of HART with conventional irradiation, 50 NSCLC patients treated by conventional fractionated irradiation (CFI) during the same period were chosen as the basis to evaluate relative effects of HART. They derived from the control group of another clinical trial of hyperfractionated irradiation for NSCLC in the same department. They received median tumor dose of 63.9 Gy (62.8-65.0)/34 fx (32-36), 48 days (45-53). RESULTS: 1. Acute and late complications: (a) In HART, 87% of patients (52 cases) developed acute radiation esophagitis: Grade 1-2, 46 cases (77%) and Grade 3, 6 cases (10%), at 2.5 weeks (2-3.5 weeks) after HART began. Five patients with Grade 3 esophagitis had their HART interrupted for <7 days. In CFI, esophagitis was much less (44%,p < 0.05) with 38% of Grade 1-2 and 6% of Grade 3. (b) In HART, acute pulmonary symptoms (RTOG Grade 1-2) occurred in 17% (10 cases), and acute radiation pneumonitis (Grade 3), in 8% (5 cases), while in CFI, they were 24% and 2% (p > 0.05), respectively. Late lung fibrosis (RTOG Grade 1-2) appeared in 20% (12 cases), whereas 18% in CFI (p > 0.05). (c), No other severe acute or late complications have been observed so far in HART. 2. Immediate response. In HART, 20% of patients (12 cases) achieved CR, 60% (36 cases), PR and 20% (12 cases), NR or PD. In CFI, the above three percentages were 10, 28, and 62%, respectively (p < 0.001). 3. Follow-up. The 1-, 2-, and 3-year actuarial survivals were 72, 47, and 28% for HART, and 60, 18, and 6% for CFI, respectively (p < 0.001). Better local control was seen in HART than in CFI with 1-, 2-, and 3-year local control rates being 71, 44, 29%, and 60, 20, and 5%, respectively (p = 0.001). Distant metastases developed less in HART than in CFI. The 1-, 2-, and 3-year distant metastasis rates were 23, 36, and 50% in HART, but 30, 48, and 80% in CFI (p = 0.021). CONCLUSION: 1. HART could be tolerated by most of the favorable NSCLC patients. The predominant complication was acute esophagitis. No other severe acute or late complications have been observed so far. 2. HART resulted in better survivals and local controls, and less distant metastases than CFI.

An epidemiological study of influenza viruses among Chinese farm families with household ducks and pigs.

To examine the possibility of interspecies transmission and genetic reassortment of influenza viruses on farms in Southern China, we surveyed 20 farm families living outside the city of Nanchang who raised pigs and ducks in their homes. Weekly interviews of family members and virus isolation studies of throat swabs and faecal samples, collected from September 1992 to September 1993, established the seasonal pattern of respiratory tract infections in these families and identified 11 influenza viruses (6 in humans and 5 in ducks). Most of the human isolates were type A of H3N2 subtype. Serologic studies of farm pigs indicated infection by the same human viruses circulating in family members, but there was no evidence that either swine or avian viruses had been transmitted to pigs. Eight of 156 human serum samples inhibited the neuraminidase activity of two of the duck isolates, raising the possibility of interspecies transmission of these avian viruses. Genotype analysis of duck and human isolates provided no evidence for reassortment. Our finding support the concept that intermingling of humans, pigs and ducks on Chinese farms is favourable to the generation of new, potentially hazardous strains of influenza virus.

Topographic organization of corticospinal projections from the frontal lobe: motor areas on the medial surface of the hemisphere.

We examined the topographic organization of corticospinal neurons in the four premotor areas on the medial wall of the hemisphere of macaques. These motor areas include the supplementary motor area (SMA) and three areas buried within the cingulate sulcus: the caudal cingulate motor area on the dorsal bank (CMAd), the caudal cingulate motor area on the ventral bank (CMAv), and the rostral cingulate motor area (CMAr). In one set of animals, we injected one fluorescent tracer into lower cervical segments of the spinal cord and another fluorescent tracer into lower lumbosacral segments to define the topographic organization of arm and leg representation within each premotor area. Similarly, in another set of animals, we injected different tracers into upper cervical and lower cervical segments to provide an indication of the topographic organization of proximal and distal arm representation within the arm representation of each premotor area. We found that all four of the premotor areas on the medial wall project to cervical and lumbosacral segments of the spinal cord. Three of these areas (SMA, CMAd, and CMAv) are like the primary motor cortex in having distinct arm and leg representations. The arm representation in each of the four motor areas on the medial wall contains separate regions that project densely to upper or to lower cervical segments. This observation suggests that each motor area contains distinct proximal and distal representations of the arm. Surprisingly, the size of the distal representation is comparable to or larger than the size of the proximal representation in each motor area. Thus, contrary to some previous hypotheses, the anatomical substrate exists for the premotor areas on the medial wall to be involved in the control of distal, as well as proximal arm movements. Our results provide a new map for guiding the exploration of the motor functions of the medial wall of the hemisphere. Furthermore, the observations of the present study support our suggestion that each of the premotor areas may be an important source of descending commands for the generation and control of movement.

Topographic organization of corticospinal projections from the frontal lobe: motor areas on the lateral surface of the hemisphere.

We examined the topographic organization of corticospinal neurons in the primary motor cortex and in the two premotor areas on the lateral surface of the hemisphere [i.e., the dorsal premotor area (PMd) and the ventral premotor area (PMv)]. In two macaques, we labeled corticospinal neurons that project beyond T7 or S2 by placing crystals of HRP into the dorsolateral funiculus at these segmental levels. In another seven macaques, we labeled corticospinal neurons that project to specific segmental levels of the spinal cord by injecting the fluorescent tracers fast blue and diamidino yellow into the gray matter of the cervical and lumbosacral segments. In one set of experiments (n = 2), we defined the representations of the arm and leg in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other fluorescent tracer into lower lumbosacral segments (L6-S1) of the same animal. In another set of experiments (n = 5), we defined the representations of distal and proximal parts of the forelimb in each cortical motor area by injecting one of the two fluorescent tracers into lower cervical segments (C7-T1) and the other tracer into upper cervical segments (C2-C4) of the same animal. In the primary motor cortex and the PMd, cortical regions that project to lower cervical segments were largely separate from those that project to lower lumbosacral segments. In the PMv, few neurons were labeled after tracer injections into lower cervical segments or lower lumbosacral segments. However, corticospinal neurons were labeled in the PMv after tracer injections into upper cervical segments and after HRP placement in the dorsolateral funiculus at T7. The region of the PMv that projects to upper cervical segments was separate from that which projects below T7. Cortical regions that project to upper and lower cervical segments of the spinal cord overlapped considerably in the primary motor cortex and in the PMd. Despite this overlap, we found that the regions of the primary motor cortex and PMd that project most densely to upper cervical segments were largely separate from those that project most densely to lower cervical segments. Furthermore, we found two separate regions within area 4 that send corticospinal projections primarily to the lower cervical segments. One of these regions was located within the classical "hand" area of the primary motor cortex. The other was located at the medial edge of arm representation in the primary motor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Elaboration of cellular DNA breaks by hydroperoxides.

Cellular damage produced by ionizing radiation and peroxides, hydrogen peroxide (HOOH) and the organic peroxides tert-butyl (tBuOOH) or cumene hydroperoxide (CuOOH) were compared. DNA breaks, toxicity, malondialdehyde production, and the rate of peroxide disappearance were measured in a human adenocarcinoma cell line (A549). The alkaline and neutral filter elution assays were used to quantitate the kinetics of single and double strand break formation and repair (SSB and DSB), respectively. Peroxides, at 0.01-1.0 mM, produce multiphasic dose response curves for both toxicity and DNA SSBs. Radiation, 1-6 Gy, produced a shouldered survival curve, and both DNA SSB and DSBs produced in cells x-rayed on ice were nearly linear with dose. The peroxides produced more SSBs than radiation at equitoxic doses. X-ray induced DNA single strand breaks were rejoined rapidly by cells at 37 degrees C with approximately 80% of initial damage repaired in 20 min. Peroxide induced SSBs were maximal after 15 min at 37 degrees C. Rejoining proceeded thereafter, but at a rate less than for x-ray induced strand breaks. Significant DNA DSBs could not be achieved by peroxides even at concentrations 50-fold higher than required to produce SSBs. HOOH treatment of DNA on filters following cell lysis and proteolysis produced SSBs. CuOOH and tBuOOH produced no SSBs in lysed cell DNA. None of the peroxides produced DSBs when incubated with lysed cell DNA. Malondialdehyde was released from cells incubated with organic hydroperoxides, but not HOOH, nor up to 40 Gy of x-rays. HOOH was metabolized three times faster than the organic peroxides. The overall results demonstrate the necessity for a metabolically active cell environment to elaborate maximal DNA strand breaks and cell death at hydroperoxide concentrations of 10(-4) or greater, but prevent strand breaks and stimulate cell growth at 10(-5) M.

[Effect of albendazole and pyrantel in treating intestinal helminthiasis and controlling the recurrence of hookworm infections].

A total of 720 human intestinal helminthic infections were divided into 4 groups and treated with albendazole 400mg/d x 3d, 400mg/d x 5d, pyrantel 1,500mg/d x 3d, or 1,500mg/d x 5d. Half a month after treatment, the negative rates of hookworm egg were 98.6, 98.6, 86.2 and 93.5%, those of ascaris egg were 96.5, 98.2, 92.9 and 96.3%, and those of whipworm egg were 86.4, 89.0, 68.9 and 67.0% respectively. Reduction rate of hookworm egg reached more than 98% in all the 4 groups. Six months after treatment, however, the positive rates of all the 4 groups rose again in varying degrees. The predominant species of hookworm infections was Necator americanus before the treatment and Ancylostoma duodenale after the treatment. It was demonstrated that the recurrence of hookworm infection resulted from A. duodenale infections, while a single dose of 400mg albendazole per day for 3 or 5 days showed good effect in controlling the recurrence of hookworm infections in a certain area.

Potentiation of radiation effects on multicellular tumor spheroids (MTS) of HeLa cells by lonidamine.

Lonidamine is a potent inhibitor of spermatogenesis and a hyperthermic sensitizer. The previous study of lonidamine and radiation using two murine tumors demonstrated that tumor cure rates were significantly increased by radiation and concomitant lonidamine. In an effort to determine the radiobiologic factors involved with the potentiating effect of radiation by lonidamine, a series of cell culture studies were carried out using multicellular tumor spheroids (MTS) of HeLa Cells. When the MTS were treated with lonidamine in combination with fractionated irradiation, remarkable enhancement of growth inhibition was observed at the drug concentration of 10 micrograms/ml. On the other hand, there was no demonstrable enhancement of growth inhibition induced by a single dose of irradiation. Although the present findings would be consistent with the inhibitory action of potentially lethal damage repair of radiation by the drug, an alternative possibility is that the cells that have received the combined treatment have undergone a metabolic change, which has altered their sensitivity to the growth inhibitory effects of lonidamine. Based on the studies reported here and in mice, it is suggested that continued drug exposure over a prolonged period may provide an enhanced therapeutic effect, even in tumor varieties where the drug has no apparent antitumor activity on nonirradiated cells.

Radiation survival properties of cultured human gastric adenocarcinoma cells and the effect of AT-1727.

Tumor cells (SGC-7901) obtained from a human gastric adenocarcinoma have been examined with regard to their intrinsic sensitivity to gamma-irradiation and as to how this intrinsic sensitivity might be altered by growth in a synthesized agent AT-1727 (N4-morpholino-methyl-3,5-dioxopiperazynyl-1,2 ethanl). Clonogenic survival was measured via colony formation assays and fitted to single-hit-multitarget formula. Exponentially growing cells exhibited the mean of survival parameters: D0 = 0.86 + 0.04 Gy; n = 7.03 + 2.3; Dq = 1.63 + 0.23 Gy and SF2 (surviving fraction of conventional daily clinical dose of 2 Gy) = 45-50%. Split-dose survival assays and delayed plating methods were used to exploit the capacity of sublethal damage repair of this cell line studied demonstrating the reappearance of initial shoulder on the survival curve and an increased survival. Alteration of radiosensitivity of SGC cells by AT-1727 was shown when cultures were incubated in a medium with the drug for a 6 hr interval between split dose irradiation, indicating the inhibition of sublethal damage repair. The radioresistance of hypoxic SGC cells was decreased when pre-treatment with AT-1727 was given 2 hr before irradiation, and the decrease of surviving fraction was drug-dose dependent. A maximum enhanced effect was obtained when 0.15 mM of AT-1727 was used, reaching an ER of 1.24. Inhibition of sublethal damage repair and action as a hypoxic radiosensitizer were considered to be two parts of the mechanism of AT-1727 in modification of radiation effects.

Gossypol, a hyperthermic sensitizer of HeLa cells.

Gossypol, a polyphenolic aldehyde extracted from cotton plants, is a potent antifertility agent in humans. Since we have previously reported that several male antifertility agents including 5-thio-D-glucose and lonidamine demonstrate hyperthermic sensitizing effects in HeLa cells, we wished to determine whether gossypol also exhibits the hyperthermic sensitization. Gossypol was not cytotoxic up to 4 h at 37 degrees C (10 micrograms/ml). When HeLa cells were exposed to gossypol at 41 degrees and 42 degrees C, significant potentiation of hyperthermia induced cytotoxicity was observed. The magnitude of the potentiation was dependent on the drug concentration, pH of the culture medium, glucose concentration, temperature, and duration of treatment. The hyperthermic sensitizing effect of gossypol was increased by an acidic pH and glucose deprivation. These data suggest that the sensitizing effect of the drug may be mediated through the lowering of cellular energy level by the inhibition of both glycolysis and oxidative phosphorylation.