GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils.

We examined GH and GH receptor expression in human leukemic cell lines and leukocytes of normal subjects to elucidate the cell types expressing GH and GH receptor, the individual variations of their expressions, their correlation and the relationships with serum IgG and IGF-I concentrations. In addition, the expression of GH secretagogue receptor, which enhances GH secretion from the anterior pituitary by synthetic GH secretagogues and that of its endogenous ligand, ghrelin, were also examined in these immune cells. GH expression in human leukemic cell lines was observed mainly in B cell lines at both the mRNA and protein level [3.8 +/- 0.2 pg/10(6) cells in Raji and 19.9 +/- 3.3 pg/10(6) cells in Daudi vs. negligible in T cell lines (Jurkat and Hut-78) and in myeloid cell lines (K-562 and HL-60)]. B cells in normal subjects were also found to be the major immune cells expressing GH mRNA, with significant individual variation. GH receptor mRNA expression was detectable in all human leukemic cell lines, although the expression level varied widely among the cell lines and was weaker than that in the liver. On the other hand, GH receptor mRNA expression was mainly found in B cells, with marked individual variation in normal subjects. There was a positive correlation between the mRNA expressions of GH and GH receptor in B cells of normal subjects (r = 0.89; P < 0.001). Single cell RT-PCR revealed that some B cells expressed both GH and GH receptor transcripts, and others expressed only GH. GH/GH receptor expression levels in B cells did not show any correlation with serum IgG and IGF-I levels in normal subjects. Expression of GH secretagogue receptor and ghrelin was detectable in all immune cells regardless of the maturity and cell types with great individual variations. In summary, GH secreted from B cells may act locally on their own receptors, and their variable expressions may be related to individual immune functions. Widespread distribution of ghrelin and GH secretagogue receptor in human immune cells may indicate unknown biological functions other than enhancing GH secretion in the immune system.

Global, regional, and local measures of complexity of multichannel electroencephalography in acute, neuroleptic-naive, first-break schizophrenics.

BACKGROUND: Schizophrenic symptoms commonly are felt to indicate a loosened coordination, i.e. a decreased connectivity of brain processes. METHODS: To address this hypothesis directly, global and regional multichannel electroencephalographic (EEG) complexities (omega complexity and dimensional complexity) and single channel EEG dimensional complexities were calculated from 19-channel EEG data from 9 neuroleptic-naive, first-break, acute schizophrenics and 9 age- and sex-matched controls. Twenty artifact-free 2 second EEG epochs during resting with closed eyes were analyzed (2-30 Hz bandpass, average reference for global and regional complexities, local EEG gradient time series for single channels). RESULTS: Anterior regional Omega-Complexity was significantly increased in schizophrenics compared with controls (p < 0.001) and anterior regional Dimensional Complexity showed a trend for increase. Single channel Dimensional Complexity of local gradient waveshapes was prominently increased in the schizophrenics at the right precentral location (p = 0.003). CONCLUSIONS: The results indicate a loosened cooperativity or coordination (vice versa: an increased independence) of the active brain processes in the anterior brain regions of the schizophrenics.

Expression of truncated midkine in human colorectal cancers.

Midkine (MK) is a growth differentiation factor originally found as the product of a retinoic acid-responsive gene. The expression of MK was examined in 35 surgically resected specimens of primary colorectal cancer using the reverse transcription-polymerase chain reaction (RT-PCR). All of the cancerous tissues expressed MK. In 5/25 cancerous tissues a truncated form of MK, which was recently found in various human tumor cell lines, was detected in addition to the full-size MK. In contrast, the truncated from of MK could not be detected in non-cancerous tissues, whereas the wild-type form was detected in 8/10 non-cancerous tissues. These results suggest that the expression of the truncated form of MK may be associated with tumorigenesis.

Reconstruction of the hepatic vein to the prosthetic inferior vena cava in right extended hemihepatectomy with ex situ procedure.

BACKGROUND: Ex situ procedure permits complete resection of a tumor involving the confluence of the three main hepatic veins, which is difficult when conventional technique is used. METHODS: We report treatment of a patient with intrahepatic cholangiocellular carcinoma involving this confluence of the three main hepatic veins and the retrohepatic inferior vena cava (IVC) by using right extended hemihepatectomy and resection of the retrohepatic IVC with ex situ procedure. Reconstruction of the left hepatic vein required anastomosis of the left hepatic vein and a polytetrafluoroethylene (PTFE) replacement for the IVC. To our knowledge this is the first report of reconstruction of the hepatic vein by use of a PTFE prosthesis. RESULTS: Anastomosis of the left hepatic vein to the PTFE graft was successfully performed during extracorporeal liver operation. The patient has had no recurrence during 8 months since the operation. Neither torsion nor obstruction of the hepatic vein and the graft has been observed. CONCLUSIONS: Reconstruction of main hepatic veins and the PTFE graft as the replacement of the IVC under extracorporeal liver operation may be useful in improving the cure rate and resection rate for liver cancer that is unresectable by the conventional technique.

Multichannel EEG fields during and without visual input: frequency domain model source locations and dimensional complexities.

27-Channel EEG potential map series were recorded from 12 normals with closed and open eyes. Intracerebral dipole model source locations in the frequency domain were computed. Eye opening (visual input) caused centralization (convergence and elevation) of the source locations of the seven frequency bands, indicative of generalized activity; especially, there was clear anteriorization of alpha-2 (10.5-12 Hz) and beta-2 (18.5-21 Hz) sources (alpha-2 also to the left). Complexity of the map series' trajectories in state space (assessed by Global Dimensional Complexity and Global OMEGA Complexity) increased significantly with eye opening, indicative of more independent, parallel, active processes. Contrary to PET and fMRI, these results suggest that brain activity is more distributed and independent during visual input than after eye closing (when it is more localized and more posterior).

Source localization of EEG activity during hypnotically induced anxiety and relaxation.

The engagement of different brain regions which implement subjectively experienced emotional states in normals is not completely clarified. Emotional states can conveniently be induced by hypnosis-based suggestions. We studied brain electric activity during hypnotically induced anxiety and relaxation in 11 right-handed normals (5 males, 6 females, mean age 26.5+/-7.6 years). After induction of light hypnosis, anxiety and then relaxation was suggested using a standardized text (reverse sequence in half of the subjects). Nineteen-channel, eyes-closed EEG (20 artifact-free s/subject) was analyzed (source localization using FFT approximation and low resolution electromagnetic tomography, LORETA). Global tests revealed the strongest difference (P<0.005) between EEG source gravity center locations during the two emotional states in the excitatory beta-2 EEG frequency band (18.5-21 Hz). Post hoc tests showed that the sources were located more right during anxiety than during relaxation (P=0.01). LORETA specified that anxiety showed maximally stronger activity than relaxation in right Brodmann area 10, and relaxation showed maximally stronger activity than anxiety in left Brodmann area 22. Clearly, the two induced emotional states were associated with activity of different neural populations. Our results agree with reports on brain activity shifted to the right (especially fronto-temporal) during negative compared with positive emotions, and support the role of beta-2 EEG frequency in emotional states.

A human monoclonal antibody derived from axillary lymph nodes of a breast cancer patient reactive to a sulfated glycolipid.

A human monoclonal antibody, BMMK-33G, was established by a fusion of human B-lymphoblastoid cells, HO-323, with lymphocytes of axillary lymph nodes obtained from a breast cancer patient. High-performance thin-layer chromatography (HPTLC)-immunostaining and enzyme-linked immunosorbent assay (ELISA) revealed that BMMK-33G was interestingly directed to enough sulfatide (Galactosylceramid-I2-sulfate), which is one of the sulfate ester containing glycolipids. By immunohistochemical staining, BMMK-33G intensely reacted to breast cancer, pancreatic cancer and gastric cancer. It also reacted to many normal human tissues including mammary glands, but these stainings were weaker than those for cancer. This report describes BMMK-33G, a human monoclonal antibody against sulfatide which may be very useful for studying not only tumor immunology but also autoimmune diseases.

[Carbon-11 labeled diacylglycerol for signal transduction imaging: effect of the solubilizer on the distribution and radiation dosimetry].

Carbon-11 labeled diacylglycerol (11C-DAG) has been developed as a signal transduction imaging agent for the CNS, and it can visualize the second messenger. For clinical application by positron CT (PET), the 11C-DAG solution must be prepared for intravenous injection. However, the 11C-DAG does not dissolve in water because of its lipophilicity and requires a solubilizer such as human serum albumin (HSA) and Tween 80 (TW-80). We examined the influence of these solubilizers on the tissue distribution of 11C-DAG, and estimated the radiation dosimetry. In the brain, uptake of 11C-DAG dissolved with HSA was 1.3-1.8 times higher than that of dissolved with TW-80. On the other hand, the lung and spleen showed a higher uptake of 11C-DAG using TW-80 than when using HSA. Especially, the lungs showed 20-40 times higher uptake than when using HSA. Also, the washout of radioactivity from tissue was slower, and the dose of radiation exposure was estimated to be higher, with TW-80 than with HSA. Therefore, between TW-80 and HSA with different solubilizing mechanisms, the later was suggested to be a better solubilizer of 11C-DAG.

[Carbon-11 labeled diacylglycerol for signal transduction imaging by positron CT: evaluation of the quality and safety for clinical use].

To elucidate the synaptic transmission in the neural system, we have been developing fundamental studies for intracellular signaling. For clinical application of carbon-11 labeled diacylglycerol (1-[1-11C]butyryl-2-palmitoyl-rac-glycerol: 11C-DAG) using positron emission computed tomography (PET), we evaluated the quality and the safety of 11C-DAG as the solution for injection. As a result, 11C-DAG was synthesized within 50 minutes, including the preparation step for injection. The half life time and energy spectrum of 11C-DAG were the same as the physical character of carbon-11, and other radioisotopes were not detected. In the quality control, 11C-DAG solution was negative in the examination of bacterial contamination and the pyrogen test in three successive synthesis procedures. In the acute toxicity test by administration of 11C-DAG and 100 mumol/kg of non-radioactive DAG to the rat intravenously, the systemic condition of the rat was not changed and no abnormalities were found in any organ 24 hours after administration. These findings indicated the safety of 11C-DAG solution. Clinical application of 11C-DAG using positron emission tomography may be useful to elucidate the dysfunction of intracellular signaling in disorders of higher cortical function such as Alzheimer disease.

[Fluorine-18 labeled 6-fluoro-L-dopa: systematization and evaluation of its usefulness].

6-[18F]Fluoro-L-dopa (L-3,4-dihydroxy-6-[18F]fluorophenylalanine; 6-[18F]FDPA) is useful to assess presynaptic dopamine metabolism in central nervous system. In this paper, we report on the usefulness of the 6-[18F]FDOPA synthesis system developed for the routine synthesis. This system consists of the 6-[18F]FOPA synthesis and the separation units in conjunction with controller using a personal computer. The synthesis time of 6-[18F]FDOPA was 73 minutes. The typical yield and specific activity were 1.4-2.4 GBq and 244-270 MBq/mumol at the end of synthesis, respectively, under the irradiation condition of 50 microA for 130 minutes. The radiochemical yields of 6-[18F]FDOPA were 31.3-38.7% based on the [18F]acetylhypofluorite, and the results were affected with the condition of potassium acetate (AcOK) to produce gaseous [18F]acetylhypofluorite. This system is useful for the routine production of 6-[18F]FDOPA because of its high yield and high specific activity while maintaining AcOK in good condition, and decreasing the radiation exposure for chemist.

[Combination with intra-hepatic arterial infusion of low-dose cisplatin and oral administration of high-dose doxyfluridine in patients with liver metastases of gastric cancer].

Two cases of gastric cancer with multiple liver metastases were treated with 5'-DFUR and CDDP after the surgery. The first case, a 79-year-old male, was administered 1,200 mg/day of 5'-DFUR orally, 6 mg/day of CDDP continuously for 2 weeks, then 20 mg once a week for 5 months by intra-hepatic arterial infusion. This case showed 95% tumor reduction by CT. The other case, a 78-year-old female, was administered 1,200 mg/day of 5'-DFUR orally and 20 mg of CDDP once a week through the hepatic artery. Following several intra-hepatic arterial infusions, it was changed to intra-venous infusion of 20 mg of CDDP twice a week because of trouble with the vascular access system. Two months after, CT showed a 46% tumor reduction in her liver. Neither complained of diarrhea nor nausea, but there was a mild degree of appetite loss. Combination with high-dose 5'-DFUR and low-dose intra-hepatic arterial infusion of CDDP is considered a very effective chemotherapy which can be performed ambulatorily while maintaining the quality of life of patients with liver metastases of gastric cancer.

[Evaluation of prophylactic hepatic arterial infusion chemotherapy after hepatectomy for metastases from colorectal cancer--the second report].

We followed 18 patients who underwent curative hepatectomy for metastatic carcinoma of the colon from March 1993 to March 1995, and investigated their survival and the effect of treatment on recurrence. The patients were randomly divided into two groups. Group A (n = 9) was given continuous 5-FU (500 mg x 4 days/week) for six weeks from 2 weeks after surgery via the hepatic artery and Group B (n = 9) was given 5-FU orally from 2 weeks after surgery. The cumulative one-, two-, and three-year survival was 88.9, 88.9, and 76.2% in Group A, while the one- and two-year survival was 100 and 80% in Group B. The one-, two-, and three-year disease-free survival was 77.8% in Group A, while the one- and two-year disease-free survival was 55.6 and 29.6% in Group B (p = 0.0369: Mantel-Cox). These findings suggest that continuous hepatic artery infusion of 5-FU is effective against post-hepatectomy recurrence of metastatic carcinoma of the colon.

[A case of locally advanced breast cancer treated with hyperthermia in combination with radiotherapy].

A 59-year-old woman was admitted to our hospital because of massive bleeding from a right breast tumor. The breast tumor had existed for ten years occupied the entire right breast (23 x 20 cm), its central part forming an ulcer 17 x 15 cm in size. Radiotherapy to the right breast and medication with tamoxifen were started, after which five courses of CMF chemotherapy were given. The tumor decreased to 16 x 14 cm, and hyperthermia to the right breast was performed for a total of 87 sessions from January 1999. The irregular protruding portion of the ulcer caused the necrosis, and was sloughed off about one month after hyperthermia. No viable tumor cells were observed in a biopsy taken at 5 months after the start of treatment (40 sessions). A total of 87 hyperthermia sessions were performed, and the ulcer disappeared. For 15 months after the end of hyperthermia, the patient showed a continuous CR. Hyperthermia in combination with radiotherapy or chemotherapy for breast cancer may produce a remarkable effect as in the present case, and may become one choice for medical treatment of locally advanced or recurrent breast cancer.

[A case of intra-arterial infusion chemotherapy for liver metastases of breast cancer].

A 55-year-old woman was seen in our clinic for liver metastases of breast cancer. She underwent a standard radical mastectomy in June, 1987. Five years and 3 months after the operation, multiple bone metastases were found on bone scintigram and 10 years after the operation multiple liver metastases on CT. She was treated with a combination of intra-arterial chemotherapy using 20-30 mg/body epirubicin every 2 weeks and chemo-endocrine therapy using medroxyprogesterone acetrate (MPA) 600 mg/day + 5'-DFUR 600 mg/day. The treatment seemed to be very useful. The liver metastases regressed by 99% in size, and the duration of response was 9 months. Bone metastases did not progress from the treatment.

[Intra-arterial infusion chemotherapy for recurrent breast cancer via an implantable system].

Intra-arterial infusion chemotherapy via implantable port catheter has been applied in 14 patients suffering from recurrent breast cancer. The regimen consisted of at least 2 cycles of epirubicin (1 cycle: 150 mg) and subsequent maintenance infusion (30 mg/2 weeks). The results were as follows: 1) The response rate (CR+PR) was 50%: 42.9% CR, 7.1% PR, 14.3% MR, and the median duration of response was 6 months. 2) Intractable pain, severe lymphedema and infection were reduced in 42.9% (6/14). 3) Leucopenia was the dose-limiting factor, and it appeared with an incidence of 78.8%. Catheter or portal trouble was observed in 28.6% of the patients. Despite the existence of several unanswered questions, intra-arterial infusion chemotherapy via implantable system is promising with regard to therapeutic effect and quality of life.

[Evaluation of prophylactic intra-hepatic-arterial infusion chemotherapy after resection of hepatic metastases from colorectal primaries].

To prevent recurrence in the residual liver after surgical treatment for colorectal metastases, the efficacy of intermittent or continuous intra-hepatic-arterial chemotherapy was analyzed. The three- and five-year survival rate of patients with intermittent infusion of ADM or MMC (n = 11) was 36.4% and 36.4%, respectively, while the survival rate of the patients without the regional chemotherapy (n = 32) was 41.9% and 23.3%, respectively, indicating no statistical significance. On the other hand, one patient out of 8 with continuous infusion of 5-FU and 2 patients out of 6 without local chemotherapy developed recurrent disease during the median follow-up time of 12 months. No serious complication such as sclerotic cholangitis or hepatic necrosis was observed. Although the follow-up was not long enough to accurately evaluate the efficacy, local chemotherapy with continuous infusion of 5-FU could be a promising method as an adjuvant chemotherapy after hepatic resection for colorectal metastases.

[Intra-arterial infusion chemotherapy for recurrent breast cancer via an implantable system--the second report].

Intra-arterial infusion chemotherapy via an implantable port catheter has been applied in 16 patients with locally recurrent breast cancer. The regimen consisted of induction and subsequent maintenance: intra-arterial infusion of epirubicin (EPI). Non-responders were entered into the second-line regimen consisting of Methotrexate and 5-FU (MF). The results were as follows: 1) The response rate (CR+PR) of EPI to locoregional lesions was 50%, and the median duration of response was 5.7 months. 2) The response rate and the duration of response of MF were 25% and 3 months, respectively. 3) Patients with ER-rith, no previous therapy and a long disease-free interval tended to have a high rate of response to intra-arterial infusion therapy. 4) Improvements of QOL, such as intractable pain, infection and severe lymphedema were recognized in 68.6% of the cases. In more than half of the cases, these treatments were carried out in an outpatient clinic. 5) Leucopenia and catheter or portal problems were encountered in 68.6% and 25.0%, respectively. We conclude that intra-arterial infusion chemotherapy via implantable system is a promising modality with regard to therapeutic effect and improvement of quality of life.

[Neoadjuvant intra-arterial infusion chemotherapy for the treatment of locally advanced breast cancer with remote metastases].

Intra-arterial infusion chemotherapy (I.A.) before the operation was performed in 7 advanced breast cancers with remote metastases. The locations of remote metastases were bone (6 cases), lung (one case), and brain (one case). The response rate of primary lesions to I.A. was 71% and the responders of remote metastases were two cases, of which one was CR (lung). After the chemotherapy, all cases underwent standard radical mastectomy, and five of seven cases are alive at this writing without local recurrence. We have performed I.A. for locally advanced breast cancer with remote metastases on the grounds that the effect of this treatment is "semi-local and semisystemic," I.A. bring down-staging to the primary lesions and can control local recurrence. The effect of the drug which leaks from I.A. is expected to the metastatic lesions. I.A. was considered to be useful too for the treatment of locally advanced breast cancer with remote metastases in terms of the excellent control effect of the local lesions and the effect on the metastatic lesions.

[A case of advanced gastric cancer successfully treated with resection after FEP (5-FU, epirubicin, CDDP) combined chemotherapy].

We reported an experience with an advanced gastric cancer patient with direct invasion into liver and metastases to liver, who had responded extremely well to an FEP combined chemotherapy. He had curatively undergone total gastrectomy with partial hepatectomy and enlarged lymph node dissection. The patient received three courses of 5-FU (750 mg/m2/day, for four days, continuous infusion), epirubicin (30 mg/m2, on day 1, i.v.), CDDP (17.5 mg/m2/day, on days 1, 2, 3, 4 i.v.) every 3 weeks in our hospital. No remarkable side effect was encountered. Partial response in the primary and invasive lesions was observed by X-P, endoscopy and CTscan. Accordingly, we could perform curative resection of the stomach with lymph nodes and parts of liver. The effect (partial response) of neoadjuvant chemotherapy was confirmed by histological examinations. FEP combined chemotherapy appears useful as a neoadjuvant approach to advanced gastric cancer.

Strategy for breast conserving treatment--analysis of recurrence and prognosis after breast cosnserving treatment.

Two hundred and four patients with small breast cancer (T < or = 3.0 cm. N0 or N1a) were given breast conserving treatment (radiation group: 101, non-radiation group: 103) during the period from Feb. 1988 to Jan. 1995. Survival analysis of breast conserving treatment radiation group versus non-radiation group revealed the following: 1) Breast conserving treatment had a good prognosis, and a 5-year overall survival rate of 96.2%. 2) There was no significant difference of 5-year overall, disease-free and ipsilateral breast disease-free survival rate between the radiation group and non-radiation group. 3) Surgical margin involvement was the most significant risk factor in local recurrence after breast conserving treatment, and non-radiation was a possible risk factor. 4) Local recurrence was a significant risk factor for distant metastases after breast conserving treatment the same as node positive. These results suggested as follows: 1) Lumpectomy with a clear margin and radiation is the best choice for small breast cancer (T < or = 3.0 cm, N0 or N1a). 2) Adjuvant therapy after surgical treatment is necessary for local recurrence.