KINETIC AND HISTOLOGICAL CHANGES OF A SERIALLY TRANSPLANTED MOUSE TUMOUR

A serially transplanted mouse tumour, NT1, was studied histologically and by autoradiography using tritiated thymidine at three stages in its transplant history: after two, seventeen and twenty-seven passages. the growth rate of the tumour decreased progressively with increasing passage number, and the mean cycle time of the tumour cells increased from 21 hr to 34 hr between the seventeenth and twenty-seventh passages. Histologically the tumour changed from having an epithelial structure (second passage), to having a mixed structure with at least two histologically different regions (seventeenth passage), to having a fibrous structure (twenty-seventh passage). Radiation response experiments were carried out on the second and twenty-seventh passaged tumours, the results of which are consistent with the kinetic and histological changes.     

腺嘌呤对体外小鼠卵母细胞减数分裂的抑制

本文研究了嘌呤类物质对小鼠卵母细胞减数分裂的影响。于卵母细胞的生发泡内显微注射腺嘌呤和腺嘌呤的类似物苄基腺嘌呤可显著抑制卵母细胞的分裂的重新启动。同时发现在腺嘌呤的作用过程中,腺苷酸环化酶的激活剂氟化钠可增强其对卵母细胞的抑制作用,表明cAMP途径在小鼠卵母细胞减数分裂成熟过程中起重要作用。腺嘌呤在不同培养液中的抑制效果不一,次黄嘌呤在DMEM和EMEM中对小鼠的卵丘细胞-卵母细胞复合体(COC)和无卵丘细胞的裸卵(DO)均具有明显的抑制效应。但腺嘌呤在DMEM比在EMEM中对COC的抑制效果更强,而且腺嘌呤在DMEM中与次黄嘌呤具有协同效应,这些差别可能是由于两种培养液中不同成分如谷氨酰胺造成卵母细胞对腺嘌呤吸收差异而引起的。     

THE DISORGANIZATION OF HEPATIC CELL NUCLEOLI INDUCED BY ETHIONINE AND ITS REVERSAL BY ADENINE

The structure of nuclei and nucleoli of hepatic cells after short-term ethionine administration was investigated with the electron microscope. By 1½ hr after the injection, a distinct alteration occurred in the nucleoli which was characterized by the appearance of electron-opaque masses in the nucleolonema. After 6–8 hr, the nucleoli showed partial fragmentation into small, dense masses. Large aggregates of interchromatinic granules appeared in the nucleoplasm. Condensation of chromatin became prominent in the nucleoplasm particularly along the nuclear membrane. By 12 hr almost complete fragmentation of nucleoli had occurred. The administration of adenine or methionine at 4 hr prevented the development of nucleolar changes. Also, adenine administration at 8 hr after ethionine completely reversed the nucleolar lesion by 12 hr. After methionine administration at 8 hr, many nucleoli showed incomplete reconstruction with many twisted ropelike structures when viewed 4 hr later. Identical structures were found when adenine was given at 8 hr, and animals were sacrificed 2 hr later. On the basis of this observation, the simplified structures of nucleoli found 2 hr after adenine or 4 hr after methionine appeared to be precursors of the nucleolonema. It is suggested that nucleoli show at least two basic reaction patterns to inhibitors of RNA synthesis, one typified by actinomycin D and one by ethionine.     

CELL KINETICS IN MOUSE THYMUS STUDIED BY SIMULTANEOUS USE OF 3H-THYMIDINE AND COLCHICINE

Following an injection of ³H-thymidine to mice there is no initial incorporation in small thymocytes, only in larger ones. In the course of time small thymocytes aquire the label. Whether the delayed uptake in small thymocytes is due to a direct cell to cell transfer of labelled nuclear material from inititally labelled larger cells to small thymocytes, or whether it is due to small thymocytes being formed from larger cells by mitotic division was investigated by the administration of Colcemid® immediately after one injection of ³H-thymidine. In the absence of cell division no labelled small thymocytes appeared with time. This finding does not support the idea of a cell to cell transfer of DNA; it rather lends support to the view that small thymocytes arise by mitotic division of larger cells in the thymus. During the treatment with Colcemid® the migration of cells took place from peripheral to central cortex just like under normal conditions.     

CHANGES IN GLYCOGEN PHOSPHORYLASE ACTIVITY AND GLYCOGEN LEVELS OF MOUSE CEREBRAL CORTEX DURING CONVULSIONS INDUCED BY HOMOCYSTEINE

Glycogen phosphorylase activity and glycogen levels were investigated in the cerebral cortex of mice of two different strains under the influence of homocysteine. Control levels of glycogen and total phosphorylase activity (i. e. activity in the presence of 1 mM-AMP) were higher in the inbred strain A, whereas a higher proportion of phosphorylase in its active form (activity without 5′-AMP) was obtained in the ICR strain (probably due to slower fixation of brain in this strain). Changes occurring after the administration of homocysteine were similar in both strains. With the onset of first clonic seizures a marked increase of phosphorylase a occurred (increase 99 per cent in strain A and 46.5 per cent in ICR, respectively). During the latter phase of tonic seizures active phosphorylase a did not significantly differ from control values. Five minutes after the end of a tonic seizure, i. e. when partial recovery could already be observed, a marked decrease of active phosphorylase a in comparison with control values, was evident (decrease against control values of 45.5 per cent in strain A and 30.5 per cent in ICR, respectively). The total phosphorylase activity was not affected in strain A, whereas a slight increase during clonic seizures was seen in the ICR strain. In accordance with the enhanced activation of phosphorylase at the onset of clonic seizures, a marked decrease in glycogen levels (35-50 per cent) was observed in both strains of mice. This decrease persisted even during the 5 min recovery period. When seizures were prevented by Na phenobarbital or glycine, the activation of phosphorylase was either completely prevented (by a non-anaesthetic dose of phenobarbital) or reduced (by glycine). The present results have demonstrated that changes in glycogen metabolism occurring during homocysteine seizures differ distinctly from those previously found during seizures induced by methionine sulphoximine, a substance structurally related to homocysteine.     

CYTOKINETIC CHANGES IN THE THYMUS OF TUMOUR-BEARING AND OF DEXAMETHASONE-TREATED MICE

Changes in the cell population kinetics of the Balb/c mouse thymus were studied (a) during the growth of a syngeneic transplantable sarcoma and (b) following intraperitoneal injection of dexamethasone. The weight of the thymus fell briefly after tumour transplantation, then recovered with overshoot and eventually declined profoundly. After dexamethasone injection the weight of the thymus fell to roughly one-third of its normal value in 36 hr. Similar cytokinetic changes were observed in both sets of experiments; thymic wasting was accompanied by a small increase in thymocyte cell cycle time, a prolongation of the S-phase of the cycle, a marked decrease in the thymocyte cell production rate and a marked reduction in the growth fraction of the thymocyte population in the superficial Cortex. It is suggested that thymic atrophy in tumour bearing animals may be a stress phenomenon.     

KINETICS OF CELL RENEWAL, CELL MIGRATION AND CELL LOSS IN THE HAIRLESS MOUSE DORSAL EPIDERMIS

Forty hairless mice were given injections of tritiated thymidine every 4th hour during 10 days. At 24 hr intervals groups of four mice were killed. The numbers of labelled basal and differentiating cells were determined by autoradiography with a stripping film technique. To determine the background activity skin sections from uninjected control mice were subjected to the same stripping film procedure. Another group of hairless mice was given one single pulse labelling with tritiated thymidine. The number of labelled mitoses was scored for 12 hr after the injection. At 10, 12 and 15 hr after the injection, the numbers of labelled basal and differentiating cells were also determined. A mathematical model of cell population kinetics in the epidermis has been suggested. The results of different simulations on this model were compared with the observed results. The curve of mean grain counts under continuous labelling increased from day to day with two well-defined plateaux. The percentage of all labelled cells increased rapidly up to the 3rd day, and thereafter the curves gradually flattened off. When basal cells and differentiated cells were considered separately the labelling index of the basal cells increased rapidly for the first 3 days and then flattened off at the 100% level on the 5th day. The labelling index of the differentiating cells was low during the first 3–4 days. Then a steep increase in the percentage of labelled differentiating cells was seen, but the curve flattened off again close to the 100 % level after the 7th day. The labelled mitosis curve had its maximum 5 hr after the thymidine injection. The curve fell again to almost zero at 12 hr. Ten, 12 and 15 hr after the injection, 6, 7 and 7% respectively of the labelled cells were found in the spinous layer. It was concluded that three grains over each nucleus could be used as lower limit for considering a cell as labelled. On this basis, tritiated thymidine injections every 4th hour can be considered as continuous labelling.     

人为因素导致的盐度变化对Kinneret湖水细菌种群的影响

由于Ｋｉｎｎｅｒｅｔ湖周围的诸多盐泉被人为地导入其下游的约旦河,使得Ｋｉｎｎｅｒｅｔ湖水的盐度逐渐下降,这对作为主要工家业用水和饮用水资源的Ｋｉｎｎｅｒｅｔ湖来说是非常有价值的。然而,对湖水中的细菌来说则可能产生不同的影响。作者通过实验研究发有水盐度的变化导致细菌种群的改变,从而使我们观察到盐度与细菌之间的关系。这些结果表明,盐度变化对湖水水质保护对策和将来一段时间内湖水管理政策的制定都具有重要的     

耐氧双歧杆菌及其B-CW对荷瘤鼠TNF-α的体内诱导

本文采用放射免疫方法（ＲＩＡ）,检测荷Ｓ１８０肿瘤小鼠外周血中ＴＮＦ－α的含量,观察双歧杆菌（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ）及其细菌壁（ＣｅｌＷａｌｓｏｆＢｉｆｉｄｏｂａｃｔｅｒｉｕｍ,Ｂ－ＣＷ）的免疫调节作用,探讨其抗肿瘤机制。结果表明该菌及其Ｂ－ＣＷ均可明显地促进机体产生ＴＮＦ－α,发挥抗肿瘤作用     

胡桃楸提取液诱导Hela细胞凋亡的研究

目的：初步探讨胡桃揪提取液对Hela细胞的凋亡诱导作用。方法：通过形态学观察,琼脂糖凝胶电泳及流式细胞术（FCM）检测凋亡细胞。结果：形态学观察发现核固缩、出现凋亡小体。琼脂糖凝胶电泳可见DNA ladder条带。流式细胞仪检测有凋亡峰。结论：胡桃揪提取液可诱导Hela细胞凋亡。     

高温致神经管畸形过程中神经生长因子及其受体表达变化的观察

为进一步探讨高温致神经管畸形的机制, 本文利用我们已经建立的高温致神经管畸形金黄地鼠模型, 在神经管发育的不同阶段, 用免疫组织化学法检测了高温对神经管及其周围间充质中神经生长因子（Ｎｅｒｖｅ Ｇｒｏｗ ｔｈ Ｆａｃｔｏｒ, ＮＧＦ） 和ＮＧＦ受体 （ｔｒｋＡ） 表达的影响。结果显示： ＮＧＦ及其受体广泛分布于神经管及其周围间充质内, 并随胎龄增加而呈规律性变化, 高温处理后的胚胎神经管上皮及其周围间充质中ＮＧＦ及其受体的免疫组织化学反应不同程度的减弱。结果提示, 神经管ＮＧＦ及其受体的减少, 可能是高温致神经管畸形的一个重要因素     

CHANGES IN RESTING POTENTIAL AND ION ABSORPTION INDUCED BY LIGHT IN A SINGLE PLANT CELL

1. Effect of light on ion absorption and resting potential of theinternodal cell of Nitella flexilis was investigated under variousconditions.
2. On illumination, the resting potential increasedby about 30mVin 10^–4 M KCl and by about 60 mV in 10^–4M NaClsolution. A similar photoelectric response was also observedin 10^–3 M KCl, 10^–2 M CaCl₂ and 5 x 10^–2 MCaCl₂ solutions, but not at all in 10^–2 M KCl solution.
3. Absorption of ions by the cell took place in parallel withthelight-induced change in resting potential.
4. Red and bluelights were very effective in increasing the restingpotential,while green light was almost ineffective. These differenteffectsof color lights were in good agreement with their effectsinincreasing the osmotic value of the cell.
5. The photoelectricresponse was not affected by phenylurethane,which, on the otherhand, strongly inhibited the light-inducedion absorption.
6. Theuptake of ions by the cell from the external medium intothevacuole is assumed to proceed in two different steps: thefirstis the process involving the ion movements across theoutermostplasmalemma, and the second is that involved in thetransportof ions through the cytoplasmic layer and tonoplast.The formerprocess is considered to be influenced by the increasein restingpotential probably caused by the light absorbed bychlorophyll.The process was, however, suggested to be independentof photosynthesis.On the other hand, the latter process issupposed to be relatedto photosynthesis. A discussion was madealong this line.

(Received July 26, 1962; )     

小鼠颌下腺上皮细胞的培养及表皮生长因子的鉴定

体外培养小鼠颌下腺细胞,形态学观察可见有上皮样细胞生长。免疫细胞化学及蛋白质印迹转移分析结果表明,体外培养的颌下腺上皮样细胞可合成并分泌表皮生长因子。     

CELL POPULATION KINETICS AND DESQUAMATION SKIN REACTIONS IN PLUCKED AND UNPLUCKED MOUSE SKIN

The kinetics of cellular proliferation in plucked and unplucked dorsal skin of mice after local X-irradiation are described, in relation to the time course of the gross desquamation reaction in skin of the dorsum and of the foot.     

肾上腺素对幼龄小鼠胸腺褪黑素受体的调节

应用放射配体结合法检测幼龄小鼠胸腺褪黑素受体（ＭＲ）,并以此为实验模型研究肾上腺素（Ｅ）对胸ＭＲ的影响及作用机制。结果表明,生理浓度的Ｅ即对胸ＭＲ有明显抑制作用,其抑制效应具时间依赖性及剂量依赖性。β－肾上腺素能受体拮抗剂普萘洛尔可逆转引抑制效应,ＣＡＭＰ对ＭＲ也有明显抑制作用,表现Ｅ对ＭＲ的抑制是通过β受体而实现的。这些结果提示,Ｅ在生理情况下即对胸腺ＭＲ有调节作用。     

抗体应答期间大鼠脑和胸腺中儿茶酚胺含量的变化

目的：探讨在抗体应答期间,脑和淋巴器官中儿茶酚胺（ＣＡｓ）含量的动态变化,籍以了解免疫状态对中枢和外周ＣＡｓ神经活动的影响。方法：用绵羊红细胞（ＳＲＢＣ）免疫大鼠,在免疫后第２￣７ｄ应用高效液相色谱－电化学检测法（ＨＰＬＣ－ＥＣＤ）测定大鼠下丘脑、海马、脑干和胸腺中云甲肾上腺素（ＮＡ）、肾上腺素（Ａ）、多巴胺（ＤＡ）和高香草酸（ＨＶＡ）的含量。结果：①下且脑和海马内ＮＡ在抗体应答期间升高,而胸腺中     

CELL POPULATION GROWTH IN THE CASTRATE MOUSE PROSTATE COMPLEX: EXPERIMENTAL VERIFICATION OF COMPUTER SIMULATION

The stimulatory action of androgen on cell proliferation in the castrate mouse seminal vesicle and coagulating gland has been studied by DNA measurements in mice 14 days after castration. 100 hr after continuous androgen treatment the level of DNA had increased 2.5-fold in the seminal vesicle and coagulating gland compared with 14 days castrated controls. A mathematical model predicted this new experimental data when the parameters employed in the simulation were constrained by the results of previous experiments.     

高糖诱导小鼠囊胚Caspase-3的表达及其意义

目的探讨高浓度葡萄糖对小鼠囊胚的影响,为防治糖尿病妊娠导致胚胎发育畸形的机制进一步提供理论依据.方法用含不同浓度（0 mmol/L、7.5mmol/L、28.0 mmol/L）D-葡萄糖的培养基体外培养小鼠囊胚24h,再用免疫组织化学S-P法检测小鼠囊胚中Caspase-3的表达.结果用含高浓度葡萄糖培养基培养的小鼠囊胚Caspase-3的表达呈强阳性.结论高浓度葡萄糖对小鼠囊胚有毒性作用,可诱导小鼠囊胚细胞的凋亡,Caspase-3参与了高浓度葡萄糖诱导囊胚细胞的凋亡作用.     

MALFORMATIONS OF THE CENTRAL NERVOUS SYSTEM INDUCED BY NEUROTROPIC DRUGS IN MOUSE EMBRYOS

Out of a sample of fifteen neurotropic drugs consisting of seven antidepressants and anti-psychotics, two antianxiety drugs, one anticonvulsant, three opiates and two synthetic analgesics, twelve were found to be teratogenic for mouse embryos, causing malformations of the central nervous system. After single injections of the teratogenic dose administered at the very beginning of the ninth day of gestation, four days later, i.e. in 13-day-old embryos, the induced defects appeared to make up a recurring syndrome of malformations which consists of several abnormalities present in various frequencies either individually or in combination in the same embryos. These malformations are: exencephaly, craniorachischisis, cervical and thoraco-lumbar myeloschisis, hydrocephalic dilatation of the fourth brain ventricle, Z-shaped kinking of the spinal cord and lumbar hydromyelia. In addition, after administration of some of the drugs, branchyury or anury with or without lumbar myeloaplasia were recorded.
In general the results reported here seem to suggest that because of their possible affinity neurotropic drugs are potentially teratogenic for the embryonic central nervous system if applied at the time of the neural tube closure although it is known that there are drugs in this group which do not cause any malformations of the central nervous system and that many non-neurotropic agents do cause such malformations. Secondly, the results seem to suggest also that the position of the malformations along the cerebro-spinal axis may be depending to some extent on the pharmacological properties of the drugs tested. These conjectures are treated here as entirely provisional pending further investigations.