[Tokyo Bones Find and human experiments by the army medical school in Tokyo].

More than 100 human bones, known as the Tokyo Human Bones, were found at the previous site of the Army Medical School in Tokyo, Japan, on July 22, 1989. They were located on the northern side of the previous location of the epidemic prevention research unit of the Army Medical School, with the discovery drawing a great deal of international attention. It was suggested that these bones might be from the victims of human experiments during World War II. It was found, in 1991, by Professor Sakura Shuo in Sapporo University, that the time and location of the burial of these bones was consistent with the existence of the Army Military Medical School. Most of these bones were Chinese, Korean and Mongolian races, and they were indeed closely related to the war. At the time they had not been found to be directly related to the human experiments of the Army Medical School, but the evidence left behind on the bones did not indicate gunshot or other war wounds, but evidence of medical experiments. This incident was known as the "Tokyo Bone Incident". Based on the research data on the Tokyo Human Bones internationally in the past 30 years, in particular, the testimony from the staff of the previous Army Medical School in Tokyo and members of the previous Army Medical School in Harbin (Unit 731), it can be concluded that some relationship exists between the Tokyo Human Bones and human experiments. This suggested that the nature of research related to these human bones conducted by the Army Medical School in Tokyo was consistent with those conducted at the Army Medical School in Harbin (Unit 731).

Clinical Significance of Prehospital Telecommunication Defined as the Critical Stroke Call Pathway in Acute Ischemic Stroke Requiring Intra-Arterial Recanalization Therapy.

BACKGROUND AND PURPOSE: To reduce the door-to-puncture time, which is a prognostic factor for the clinical outcome after intra-arterial recanalization therapy, we established a prehospital telecommunication strategy between neurointerventionalists and emergency medical technicians, namely, the critical stroke call pathway. We retrospectively evaluated the clinical significance of the critical stroke call pathway by comparing the door-to-puncture time and clinical outcome of the critical stroke call pathway with those of the routine stroke pathway. MATERIALS AND METHODS: From January 2018 to June 2020, one hundred seventy-one patients with anterior circulation occlusion who underwent arterial recanalization therapy via the emergency department were included in this study. Patients were divided into the critical stroke call pathway group (n = 75, 43.9%) and the routine stroke pathway group (n = 96, 56.1%). RESULTS: The critical stroke call pathway group exhibited a shorter door-to-puncture time than the routine stroke pathway group (median, 87 minutes; interquartile range, 63-107 minutes; P < .001). On multivariable analysis, a good clinical outcome (3-month mRS, 0-2) was independently associated with a shorter door-to-puncture time (adjusted OR, 0.998; adjusted 95% CI, 0.996-1.000; P = .027). In patients with an NIHSS score on admission of ≤11, an excellent clinical outcome (3-month mRS, 0-1) was more frequently achieved in the critical stroke call pathway group than in the routine stroke pathway group (22/33, 66.7%, versus 21/48, 43.8%; P = .042). CONCLUSIONS: In our study, compared with the routine stroke pathway, the critical stroke call pathway remarkably reduced the door-to-puncture time for arterial recanalization therapy, with better clinical outcomes, especially in patients with a relatively good clinical status.

Usefulness of the Delay Alternating with Nutation for Tailored Excitation Pulse with T1-Weighted Sampling Perfection with Application-Optimized Contrasts Using Different Flip Angle Evolution in the Detection of Cerebral Metastases: Comparison with MPRAGE Imaging.

BACKGROUND AND PURPOSE: Contrast-enhanced T1-weighted sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) with the delay alternating with nutation for tailored excitation (DANTE) pulse could suppress the blood flow signal and provide a higher contrast-to-noise ratio of enhancing lesion-to-brain parenchyma than the MPRAGE sequence. The purpose of our study was to evaluate the usefulness of SPACE with DANTE compared with MPRAGE for detecting brain metastases. MATERIALS AND METHODS: Seventy-one patients who underwent contrast-enhanced SPACE with DANTE and MPRAGE sequences and who were suspected of having metastatic lesions were included. Two neuroradiologists determined the number of enhancing lesions, and diagnostic performance was evaluated using figure of merit, sensitivity, positive predictive value, interobserver agreement, and reading time. Contrast-to-noise ratiolesion/parenchyma and contrast-to-noise ratiowhite matter/gray matter were also assessed. RESULTS: SPACE with DANTE (observer one, 328; observer two, 324) revealed significantly more small (<5 mm) enhancing lesions than MPRAGE (observer one, 175; observer two, 150) (P < 0.001 for observer 1, P ≤ .0001 for observer 2). Furthermore, SPACE with DANTE showed significantly higher figure of merit and sensitivity and shorter reading time than MPRAGE for both observers. The mean contrast-to-noise ratiolesion/parenchyma of SPACE with DANTE (52.3 ± 43.1) was significantly higher than that of MPRAGE (17.5 ± 19.3) (P ≤ .0001), but the mean contrast-to-noise ratiowhite matter/gray matter of SPACE with DANTE (-0.65 ± 1.39) was significantly lower than that of MPRAGE (3.08 ± 1.39) (P ≤ .0001). CONCLUSIONS: Compared with MPRAGE, SPACE with DANTE significantly improves the detection of brain metastases.

Pointwise Encoding Time Reduction with Radial Acquisition with Subtraction-Based MRA during the Follow-Up of Stent-Assisted Coil Embolization of Anterior Circulation Aneurysms.

BACKGROUND AND PURPOSE: Time-of-flight MR angiography, though widely used after coil embolization, is associated with limitations owing to magnetic susceptibility and radiofrequency shielding following stent-assisted coil embolization. We evaluated the pointwise encoding time reduction with radial acquisition (PETRA) sequence in subtraction-based MRA (qMRA) using an ultrashort TE relative to TOF-MRA during the follow-up of stent-assisted coil embolization for anterior circulation aneurysms. MATERIALS AND METHODS: Twenty-five patients (3 men and 22 women; mean age, 59.1 ± 14.0 years) underwent stent-assisted coil embolization for anterior circulation aneurysms and were retrospectively evaluated using TOF-MRA and PETRA qMRA data from the same follow-up session. Two neuroradiologists independently reviewed both MRA findings and subjectively graded flow within the stents (relative to the latest DSA findings) and occlusion status (complete occlusion or neck/aneurysm remnant). Interobserver and intermodality agreement for TOF-MRA and PETRA qMRA were evaluated. RESULTS: The mean score for flow visualization within the stents was significantly higher in PETRA qMRA than in TOF-MRA (P < .001 for both observers), and good interobserver agreement was reported (κ = 0.63). The aneurysm occlusion status of PETRA qMRA (observer 1, 92.0%; observer 2, 88.0%) was more consistent with DSA than with TOF-MRA (observer 1, 76.0%; observer 2, 80.0%), and there was a better intermodality agreement between DSA and PETRA qMRA than between DSA and TOF-MRA. CONCLUSIONS: These findings indicate that PETRA qMRA is a useful follow-up technique for patients who have undergone stent-assisted coil embolization for anterior circulation aneurysms.

Coil Embolization in Patients with Recurrent Cerebral Aneurysms Who Previously Underwent Surgical Clipping.

BACKGROUND AND PURPOSE: Surgical revision of recurrent cerebral aneurysms is technically difficult. Therefore, coil embolization has been used as an alternative in these cases. The aim of this study was to evaluate the clinical and angiographic outcomes of coil embolization in patients with recurrent cerebral aneurysms after microsurgical clipping. MATERIALS AND METHODS: Between May 1999 and February 2016, nineteen patients with 19 recurrent aneurysms who previously underwent surgical clipping were treated by coil embolization. RESULTS: Nine patients presented with subarachnoid hemorrhage (47.4%). The interval between surgical clipping and coil embolization was 143.5 ± 66.1 months (range, 43-276 months). Single- or double-catheter coil embolization was performed in 16 patients. A balloon (n = 1) and stents (n = 2) were used to assist the coil embolization in 3 patients. Immediate radiologic findings after coil embolization showed complete occlusion in 10 patients, a residual neck in 8 patients, and a residual sac in 1 patient. Procedure-related permanent morbidity occurred in 1 patient. The mean clinical follow-up was 58.3 ± 38.8 months. Poor clinical outcomes (modified Rankin Scale score = ≥3) at the end of the clinical follow-up were reported in 5 patients (26.3%). Angiographic follow-up was available for 12 patients (63.2%). Major recurrence was detected in 5 patients (41.7%), and a tendency for aneurysm regrowth rather than coil compaction was noted in all cases. CONCLUSIONS: In our series, coil embolization for recurrent aneurysms after surgical clipping was feasible but had a high recurrence rate and tended to result in aneurysm regrowth rather than coil compaction.

[Clinical analysis of nose rhabdomyosarcoma].

Objective:To improve the diagnosis of the nose rhabdomyosarcoma.Method:Twenty-four patients with nose rhabdomyosarcoma were studied retrospectively.Result:Among 24 patients with nose rhabdomyosarcoma, three patients were in stage Ⅰ, four patients were in stage Ⅱ, eleven patients were in stage Ⅲ, and six patients were in stage Ⅳ. Embryonal rhabdomyosarcoma is the commonest in all the pathological types. Most patients need comprehensive therapy, including surgery operation, radiotherapy, and multicycle chemotherapy. Prognosis was poor in most of the cases. The survival rate of one year was 70.8% (17/24), and survival rate of three years was 30.3% (8/24).Conclusion:Different surgical protocols should be adopted for different patients, and postoperative chemoradiotherapy should be adopted for advanced treatment. By means of multidisciplinary collaboration, the patient's survival time would be prolonged.

Intra-arterial infusion of a glycoprotein IIb/IIIa antagonist for the treatment of thromboembolism during coil embolization of intracranial aneurysm: a comparison of abciximab and tirofiban.

BACKGROUND AND PURPOSE: Abciximab and tirofiban are commonly used for the treatment of thromboembolisms that form during coiling of intracranial aneurysms; however, it is not known which of these inhibitors is safer and more effective. We report the safety and the recanalization rates for intra-arterial abciximab and intra-arterial tirofiban infusion for the treatment of thromboembolisms that form during coiling. MATERIALS AND METHODS: Between March 2004 and April 2011, 346 intracranial aneurysms were treated with coiling. Thromboembolisms developed in 22 of these patients and were treated by use of intra-arterial tirofiban (n = 11) or abciximab (n = 11) infusion. RESULTS: In the abciximab group, the thromboembolisms were completely (n = 1) or partially (n = 7) resolved in 8 cases (72.7%) at the time of the final control angiography. Complete (n = 9) or partial (n = 2) resolution was achieved in all cases at the time of follow-up angiography (<3 days after the procedure). In the tirofiban group, thromboembolisms were completely (n = 4) or partially (n = 6) resolved in 10 cases (90.9%) at the time of the final control angiography. Complete (n = 9) or partial (n = 2) resolution was observed in all cases at the time of the follow-up angiography. There were no statistically significant differences between the 2 groups with respect to thrombus resolution (final angiography, P = .311; follow-up angiography, P = .707). No hemorrhagic complications developed in either group. CONCLUSIONS: These results suggest that tirofiban is more effective than abciximab for the immediate resolution of thromboembolisms, with no statistical significance. Both intra-arterial tirofiban and abciximab exhibited similar safety and recanalization rates.

Spontaneous healing of iatrogenic direct carotid cavernous fistula.

Direct carotid-cavernous fistula (CCF) by selective navigation using a microcatheter or microwire is a rare complication, and its timing of treatment has not been elucidated. We report two cases of direct CCFs resulting from injury to the cavernous posterior segment of the internal carotid artery during selective navigation. We did not plan to perform emergent endovascular treatment for these direct CCFs because no symptoms related to direct CCFs developed. Follow-up angiography revealed spontaneous healing of both direct CCFs. Close observation rather than emergent treatment may represent another option for direct CCF by selective navigation during the endovascular procedure.

The characteristics and risk factors of headache development after the coil embolization of an unruptured aneurysm.

BACKGROUND AND PURPOSE: Development of a headache after aneurysm coil embolization is not uncommon but has received little attention. The authors prospectively analyze the characteristics and risk factors of a headache after coiling in patients treated for an unruptured cerebral aneurysm. MATERIALS AND METHODS: Ninety patients treated for an unruptured cerebral aneurysm over a period of 1 year, and without a headache history within a month before coiling, were enrolled in this study. All coilings were successfully performed without neurologic complications. After coiling, headache development and intensities were recorded. RESULTS: Fifty (55.6%) patients experienced a headache (VAS score, 4.5 ± 2.02) at 7.9 (range, 0-72) hours, on average, after coiling, and all headaches resolved within an average of 73.0 (range, 3-312) hours. Univariate analysis showed that the following were significantly associated with the development of a headache: age ≤ 50 years (OR 4.636, 95% CI, 1.414-15.198), hypertension (OR 0.232, 95% CI, 0.095-0.571), a packing attenuation of >25% (OR 3.619, 95% CI, 1.428-9.174), and a previous headache history (OR 2.769, 95% CI, 1.120-6.849). However, binary logistic regression showed that only a packing attenuation of >25% (P = .013, adjusted OR 3.774, 95% CI, 1.320-10.790) and no history of hypertension (P = .019, adjusted OR 3.515, 95% CI, 1.233-10.021) were independently associated with the development of a headache. CONCLUSIONS: A headache frequently developed after the coiling of unruptured aneurysms. However, headaches were relatively benign and resolved within several days. The present study shows that no hypertension history and a packing attenuation of >25% are risk factors of headache development.

Comparison of 2-year angiographic outcomes of stent- and nonstent-assisted coil embolization in unruptured aneurysms with an unfavorable configuration for coiling.

BACKGROUND AND PURPOSE: Stents are known to have hemodynamic and biologic effects in addition to their mechanical scaffold effect. To determine whether stents affect long-term outcomes after coiling of unruptured aneurysms, we compared angiographic outcomes at 2 years postembolization for stent- and nonstent-assisted coiled unruptured aneurysms. MATERIALS AND METHODS: Stent-assisted coiling was used in unruptured aneurysms unfavorable for simple coiling (neck size >4 mm and dome-to-neck ratio <1.5) in our practice. Therefore, 126 coiled unruptured aneurysms in total (40 [31.7%] stent group and 86 [68.3%] nonstent group) with these conditions were selected for this study. The nonstent group aneurysms were treated with multiple microcatheter technique (53 cases) or balloon-assisted technique (33 cases). Self-expandable stents were used for coiling in stent group aneurysms. No significant difference in aneurysmal characteristics (aneurysm type [sidewall/bifurcation], diameter, neck size, and dome-to-neck ratio) or angiographic outcome at embolization (packing attenuation, obliteration grade, and contrast filling) were observed between the 2 study groups. RESULTS: At 2-year follow-up visits, rates of progressive occlusion (stent group, 17/40 [42.5%] versus nonstent group, 34/86 [39.5%]) and recanalization (7/40 [17.5%] versus 18/86 [21.0%]) did not show a statistically significant difference between the 2 groups (P = .895). CONCLUSIONS: The present study did not show that additional hemodynamic and biologic effects of stents designed for neck remodeling were enough to enhance progressive occlusion and prevent the recanalization of unruptured aneurysms. Our finding suggests that stent placement provides no better long-term angiographic outcomes for unruptured aneurysms with an unfavorable configuration for coiling.

Endovascular treatment for unruptured intracranial aneurysms in elderly patients: single-center report.

BACKGROUND AND PURPOSE: The optimal management of patients with unruptured intracranial aneurysms remains controversial in elderly populations. The aim of this study was to evaluate technical results and clinical outcomes in a single center of consecutive elderly patients with unruptured intracranial aneurysms treated with endovascular embolization. MATERIALS AND METHODS: Between May 2003 and February 2010, 96 patients older than 70 years (men, 16 patients; women, 80 patients; mean age, 73 years) with 122 saccular unruptured intracranial aneurysms were treated in our hospital with an endovascular approach. The endovascular procedures and technique, angiographic follow-up, and complications were evaluated. RESULTS: Successful embolizations without complications were completed in 95.9%. Five patients had procedure-related events, including thromboembolism in 1 patient, aneurysm perforation during the procedure in 1, and 3 postoperative transient minor symptoms (headache, otalgia, and trigeminal pain) in 3. The degree of occlusion of the treated aneurysm was complete in 46.7%; there was a small neck remnant in 40.9% and residual filling in 12.2%. Imaging (MR angiography) follow-up was performed in 68.7% of the patients. The mean follow-up duration was 19.4 months (range, 5-57 months). Fifty-five patients (93.9%) showed no interval change of the residual neck. Four (6%) demonstrated recanalizations, all of which were successfully recoiled. CONCLUSIONS: Endovascular treatment of unruptured intracranial aneurysms in patients older than 70 years of age appears to be safe. Favorable outcomes with low morbidities may replace surgery or conservative treatment as an active management alternative.

Is fasting necessary for elective cerebral angiography?

BACKGROUND AND PURPOSE: In order to prevent unexpected events such as aspiration pneumonia, cerebral angiography has been performed under fasting in most cases. We investigated prospectively the necessity of fasting before elective cerebral angiography. MATERIALS AND METHODS: The study is an open-labeled clinical trial without random allocation. In total, 2554 patients who underwent elective cerebral angiography were evaluated on development of nausea, vomiting, and pulmonary aspiration during and after angiography. Potential risks and benefits associated with fasting were provided in written documents and through personal counseling to patients before the procedure. The patients chose their fasting or nonfasting option. No restriction in diet was given after angiography. The patients were observed for 24 hours. Nausea and vomiting during and within 1 hour after angiography was considered as a positive event associated with cerebral angiography. RESULTS: The overall incidence of nausea and vomiting during and within 1 hour after angiography was 1.05% (27/2554 patients). There was no patient with pulmonary aspiration. No statistical difference in nausea and vomiting development between the fasting and the diet groups was found. CONCLUSIONS: The incidence of nausea and vomiting associated with cerebral angiography is low and not affected by diet or fasting. Pulmonary aspiration had no difference between the diet and the fasting group. Our study suggests that fasting may not be necessary for patients who undergo elective cerebral angiography.

Endovascular strategies for vertebrobasilar dissecting aneurysms.

BACKGROUND AND PURPOSE: Dissecting vertebrobasilar aneurysms are challenging to treat, and standard treatment modalities remain controversial. We retrospectively evaluated our experience using endovascular techniques to treat these aneurysms. MATERIALS AND METHODS: From February 1997 to December 2007, 42 patients with intradural vertebrobasilar dissecting aneurysms underwent endovascular treatment. Twenty-nine patients had ruptured aneurysms, and 13 patients had unruptured dissecting aneurysms. The endovascular modalities for vertebrobasilar dissecting aneurysms were the following: 1) trapping (n = 30), 2) proximal occlusion (n = 3), 3) stent with coil (n = 6), and 4) stent alone (n = 3). RESULTS: Seventeen of the 29 patients with ruptured vertebrobasilar dissecting aneurysms had successful outcomes without procedural complications following endovascular treatment. Procedure-related complications were the following: 1) rebleeding (n = 3), 2) posterior inferior cerebellar artery (PICA) territory infarction (n = 6), 3) brain stem infarction (n = 2), and 4) thromboembolism-related multiple infarctions (n = 1). Clinical outcomes were favorable in 32 patients (76.1%). There were 3 (7.1%) procedure-related mortalities due to rebleeding, and 1 (2.4%) non-procedure-related mortality due to pneumonia sepsis. All 13 patients with unruptured vertebrobasilar dissecting aneurysms had favorable clinical and radiologic outcomes without procedure-related complications. CONCLUSIONS: Endovascular procedures for treatment of unruptured symptomatic dissecting aneurysms resulted in favorable outcomes. Ruptured vertebrobasilar dissecting aneurysms are associated with a high risk of periprocedural complications. Risks can be managed by using appropriate endovascular techniques according to aneurysm location, configuration, and relationship with the PICA.

Heterologous expression and purification of recombinant rolipram-sensitive cyclic AMP-specific phosphodiesterases.

With the cloning of cDNAs coding for the different phosphodiesterase 4 (PDE4) isoenzymes present in mammals, homogeneous preparations of these forms have become readily available. This strategy has greatly facilitated the understanding of the properties of the myriad of isoforms derived from the four PDE4 genes found in mammals, and has opened a new avenue to develop inhibitors with a different degree of selectivity for each isoform. Here we describe the strategies and methods used to express PDE4 in bacterial, yeast, insect, and mammalian cell heterologous systems, and review the advantages and disadvantages of each of these expression strategies. In addition, procedures to purify the recombinant proteins are described. The recently developed purification of a PDE4 by immunoaffinity chromatography provides a rapid and efficient method to prepare large quantities of PDE4. This method should be very useful for structural and kinetic studies on the PDE4D isoforms.

Lip form responses to changes in maxillary incisor position.

A study was conducted to assess the measurement accuracy of a laser three-dimensional measurement system for measuring facial profile and to investigate the changes in lower facial morphology caused by experimental protrusion of the upper incisors, and also to examine the relationship between the changes in lip form and lip thickness. The study subjects were 24 Japanese male dental students attending Nihon University School of Dentistry at Matsudo, who had normal overbite, overjet, and normal occlusion, and a good facial profile. The mean age was 23.2 years with a range of 21.5 to 25.8 years. Three-dimensional measurements obtained by a computerized 3D laser scanning system were used to evaluate facial morphology. The measurement error of this system was less than 0.5 mm in any three-dimensional linear measurements. The stability and reproducibility of the recording procedure were evaluated. The changes in facial morphology caused by orthodontic treatment and orthognathic surgery were visualized in any direction by this three-dimensional graphic system. Lip thickness was not associated with changes in lip form. However, a relationship between the right and left corners of lip and lip thickness was noted. With regard to the ratio of changes in hard tissue and lips, the value of the original position for a 4 mm protrusion was not the same as that for a 4-8 mm protrusion. Also, the correlation of the changes in both groups was very low. The changes in lip thickness were associated with changes in stomion position, which in turn were related to the vertical change in the upper lip.

Differential expression of mRNA encoding interleukin-12 p35 and p40 subunits in situ.

Interleukin-12 (IL-12) is a heterodimeric cytokine that plays an important role in the regulation of the immune response. For biological activity the expression of both subunits of IL-12, p35 and p40, is required. Moreover, in the mouse the p40 chain of IL-12 specifically inhibits the effects of the IL-12 heterodimer. In the present study we have analyzed by in situ hybridization the expression of the p35 and p40 mRNA in the spleens of BALB/c and mutant (SCID, nude, beige) mice, unstimulated and after in vivo stimulation with lipopolysaccharide (LPS) and with staphylococcal enterotoxin B (SEB). In unstimulated spleens of BALB/c mice p35 and p40 mRNA were only detectable in a few strongly stained single cells, p35 mRNA was expressed in addition weakly in the B cell areas. After injection of LPS or SEB, p40 mRNA was strongly induced in the T cell areas all over the spleen, whereas expression of p35 mRNA and its distribution pattern did not change. Surprisingly, most of the mRNA for p35 and p40 was localized in different areas of the spleen and was apparently produced by different cells. In macrophage-depleted spleens the increased expression of p40 mRNA in response to LPS was reduced but still detectable, demonstrating that other cells besides macrophages can up-regulate IL-12 p40 mRNA. Nude mice showed a stronger expression of p35 mRNA, SCID mice lacked the weak p35 staining of the B cell areas but showed a strong basal expression of both p35 and p40 mRNA and a focal response to LPS. The pattern of IL-12 mRNA expression in beige mice was the same as in normal mice. These data demonstrate a spatial dissociation of expression of the two chains of IL-12 and are compatible with a regulatory role of the isolated IL-12 p40 chain in vivo. In addition, they indicate that the demonstration of mRNA for both chains of IL-12 in whole tissues or cell mixtures is not necessarily indicative of functional IL-12.

Interleukin-12/T cell stimulating factor, a cytokine with multiple effects on T helper type 1 (Th1) but not on Th2 cells.

At least two subsets of CD4+ T helper cell lymphocytes termed Th1 and Th2 exist in the mouse and probably in humans. They are characterized by the secretion of different lymphokines and by their functional behavior. Dysregulated expansion of one or the other subset may be one reason for the development of certain diseases. Thus, it is of importance to define the signals involved in the differentiation and activation of the two Th cell subsets. It is known and has been confirmed in this report that the cytokine interleukin (IL)-1 acts on Th2 cells but not on Th1 cells. We now report that a previously identified cytokine which was provisionally termed T cell stimulating factor is identical with IL-12 and exhibits a reciprocal behaviour to IL-1. IL-12 has several effects on Th1 cells. It can induce the proliferation of certain Th1 cells in combination with IL-2. Synthesis of interferon (IFN)-gamma by Th1 cells can be triggered by IL-2 plus IL-12. In contrast to the IFN-gamma production observed after T cell receptor (TcR) CD3 stimulation of Th1 cells with lectin Concanavalin A the IFN-gamma production induced by IL-12 + IL-2 is insensitive to the immunosuppressive drug cyclosporin A. Furthermore, IL-12 enhances the TcR/CD3-induced synthesis of IFN-gamma of several Th1 clones. Finally, IL-12 (+IL-2) induces homotypic cell aggregation of Th1 clones. This type of cell aggregation depends on the participation of LFA-1 and ICAM-1 molecules. In all activation systems with Th1 cells no effect of IL-1 was demonstrable. In contrast, only IL-1 but not IL-12 served as a co-stimulatory signal for several Th2 cell lines activated via the TcR/CD3 complex.