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Abstract Background The lack of sufficient specificity and sensitivity among conventional cancer biomarkers, such as prostate specific antigen (PSA) for prostate cancer has been widely recognized after several decades of clinical implications. Autoantibodies (autoAb) among others are being extensively investigated as potential substitute markers, but remain elusive. One major obstacle is the lack of a sensitive and multiplex approach for quantifying autoAb against a large panel of clinically relevant tumor-associated antigens (TAA). Methods To circumvent preparation of phage lysates and purification of recombinant proteins, we identified B cell epitopes from a number of previously defined prostate cancer-associated antigens (PCAA). Peptide epitopes from cancer/testis antigen NY-ESO-1, XAGE-1b, SSX-2,4, as well as prostate cancer overexpressed antigen AMACR, p90 autoantigen, and LEDGF were then conjugated with seroMAP microspheres to allow multiplex measurement of autoAb present in serum samples. Moreover, simultaneous quantification of autoAb plus total PSA was achieved in one reaction, and termed the "A+PSA" assay. Results Peptide epitopes from the above 6 PCAA were identified and confirmed that autoAb against these peptide epitopes reacted specifically with the full-length protein. A pilot study was conducted with the A+PSA assay using pre-surgery sera from 131 biopsy-confirmed prostate cancer patients and 121 benign prostatic hyperplasia and/or prostatitis patients. A logistic regression-based A+PSA index was found to enhance sensitivities and specificities over PSA alone in distinguishing prostate cancer from nonmalignant cases. The A+PSA index also reduced false positive rate and improved the area under a receiver operating characteristic curve. Conclusions The A+PSA assay represents a novel platform that integrates autoAb signatures with a conventional cancer biomarker, which may aid in the diagnosis and prognosis of prostate cancer and others.

In mid-September 2019, a teenage Chinese male student and part-time waiter in Tokyo was diagnosed with multidrug-resistant (MDR) sputum smear-positive pulmonary tuberculosis (TB). This study describes the outbreak investigation of his friends and colleagues at the restaurant. We investigated 6 friends and 15 colleagues; 5 friends and 13 colleagues underwent interferon-γ release assay (IGRA). Of these, 3 friends (60.0%) and 4 colleagues (30.8%) were IGRA-positive. Each of the friends and colleagues was found to have MDR-TB (20% and 7.7%, respectively). Challenges during the investigation were the unavailability of regimens for latent TB infection (LTBI) for contacts with MDR-TB, budgetary constraints concerning implementing computed tomography (CT) scans for the contacts, frequent address changes of foreign-born patients and contacts, investigation during the coronavirus disease pandemic, and variations of alphabetical expression of the names of the patients and contacts, particularly for those from China. It is recommended that the national government officially adopt prophylaxis regimens for LTBI with MDR-TB, address the budgetary constraints regarding CT scans, and deploy liaison officers for coordinating investigations involving many foreign-born patients and contacts scattered in multiple municipalities. The names of foreign-born persons could more accurately be identified using both the alphabet and Chinese characters.

Purpose: With a new tumor-tracking system (Synchrony®) for tomotherapy (Radixact®), the internal and set-up margins can be tightened, like cyberknife (CyberKnife®), in the planning of stereotactic body radiotherapy (SBRT) for prostate cancer. Recently, the usefulness of placing a hydrogel spacer between the prostate and rectum has been established in prostate radiotherapy. We evaluated the characteristics of tomotherapy plans with the tumor-tracking system and compared them with cyberknife SBRT plans for localized prostate cancer using a hydrogel spacer., Methods: In 20 patients, two plans were created and compared using tomotherapy and cyberknife. All patients underwent hydrogel spacer injection behind the prostate before simulation CT and MRI for fusion. For all plans, 36.25 Gy in 7.25-Gy fractions for a minimum coverage dose of 95% of planning target volume (PTV) (D95%) was prescribed. The D99% of PTV and D0.1 ml of the PTV, urethra, bladder, and rectum were intended to be > 90%, 110-130%, 100-110%, <110%, and <100%, respectively, of the prescribed doses., Results: All plans using tomotherapy and cyberknife achieved the intended dose constraints. The cyberknife plans yielded better median PTV-V110% (volume of PTV covered by 110% isodose line, 54.8%), maintaining lower median D0.1 ml of the urethra (37.5 Gy) and V80% of the bladder (11.0 ml) compared to the tomotherapy plans (39.0%; p < 0.0001, 38.2 Gy; p < 0.0001, and 18.3 ml; p < 0.0001, respectively). The tomotherapy plans were superior to the cyberknife plans for the rectum (V80% = 0.4 vs. 1.0 ml, p < 0.001; D1ml = 26.4 vs. 29.0 Gy, p = 0.013)., Conclusions: Our results suggested that tomotherapy with the tumor-tracking system has reasonable potential for SBRT for localized prostate cancer using a hydrogel spacer., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Ketone bodies, including β-hydroxybutyrate and acetoacetate, are important alternative energy sources during energy shortage. β-Hydroxybutyrate also acts as a signaling molecule via specific G protein-coupled receptors (GPCRs); however, the specific associated GPCRs and physiological functions of acetoacetate remain unknown. Here we identified acetoacetate as an endogenous agonist for short-chain fatty acid (SCFA) receptor GPR43 by ligand screening in a heterologous expression system. Under ketogenic conditions, such as starvation and low-carbohydrate diets, plasma acetoacetate levels increased markedly, whereas plasma and cecal SCFA levels decreased dramatically, along with an altered gut microbiota composition. In addition, Gpr43 -deficient mice showed reduced weight loss and suppressed plasma lipoprotein lipase activity during fasting and eucaloric ketogenic diet feeding. Moreover, Gpr43 -deficient mice exhibited minimal weight decrease after intermittent fasting. These observations provide insight into the role of ketone bodies in energy metabolism under shifts in nutrition and may contribute to the development of preventive medicine via diet and foods., Competing Interests: The authors declare no competing interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy-cis-12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus-colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites.

Background: We compared T-SPOT.TB (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT) test results in a contact investigation., Subjects and Methods: The index case was a male lecturer at a vocational school in Tokyo. Chest X-ray examinations and T-SPOT tests were performed on all 397 contacts, and QFT-GIT was performed on a subset of these contact subjects., Results: Chest X-ray examination showed no evidence of tuberculosis in any subjects. Among 389 contacts that underwent T-SPOT testing, 5 showed a positive reaction, 3 showed borderline reactions (1 positive borderline and 2 negative borderline), and 381 were negative. Among 56 contacts tested using both QFT-GIT and T-SPOT, 4 were positive, 1 was borderline, and 51 were negative by QFT-GIT. By T-SPOT, 2 contacts were positive, 1 was borderline positive, and 53 were negative. Preventive chemotherapy was indicated for the 5 positive and 1 borderline positive contacts identified by the T-SPOT test., Discussion: Chest X-ray examination and the T-SPOT test did not identify the TB outbreak., Conclusion: The majority of contact subjects were negative by both tests, suggesting that both have a high specificity in contact investigations. However, the moderate concordance rate indicates that further testing is necessary to fully evaluate these tests.

Purpose: Since distigmine can cause the serious side effect of cholinergic crisis, its dosage regimen has been reduced to 5 mg/day for patients with difficulty in urination due to detrusor underactivity. Therefore, the efficacy and safety of add-on therapy with distigmine at 5 mg daily were examined in patients with persistent urination problems due to detrusor underactivity despite administration of alpha1-blockers., Patients and Methods: The subjects were 39 patients with underactive bladder (18 men and 21 women with an average age of 75 years) who showed no improvement of difficulty in urination or had a residual urine volume > or = 50 ml despite the administration of alpha1-blockers for more than 4 weeks. They received treatment with distigmine (5 mg daily after breakfast) in addition to their alpha1-blockers for 8 weeks. The international prostate symptom score (IPSS), quality-of-life (QOL) score, residual urine volume, blood pressure, and biochemistry tests were investigated before and after addition of distigmine., Results: After four and eight weeks of distigmine administration, all items of the IPSS and QOL score, as well as the residual urine volume, showed a significant decrease. In contrast, the pressure and pulse rate were unchanged. Serum creatinine showed a slight but significant decreased. As adverse events, frequent defecation, fecal incontinence, diarrhea, frequent urination and poor physical condition were recognized in 4 patients, but there was no serious event., Conclusion: For difficulty in urination due to detrusor underactivity, the combination of an alpha1-blocker with distigmine at 5 mg daily showed early efficacy and good safety.

Background: The lack of sufficient specificity and sensitivity among conventional cancer biomarkers, such as prostate specific antigen (PSA) for prostate cancer has been widely recognized after several decades of clinical implications. Autoantibodies (autoAb) among others are being extensively investigated as potential substitute markers, but remain elusive. One major obstacle is the lack of a sensitive and multiplex approach for quantifying autoAb against a large panel of clinically relevant tumor-associated antigens (TAA)., Methods: To circumvent preparation of phage lysates and purification of recombinant proteins, we identified B cell epitopes from a number of previously defined prostate cancer-associated antigens (PCAA). Peptide epitopes from cancer/testis antigen NY-ESO-1, XAGE-1b, SSX-2,4, as well as prostate cancer overexpressed antigen AMACR, p90 autoantigen, and LEDGF were then conjugated with seroMAP microspheres to allow multiplex measurement of autoAb present in serum samples. Moreover, simultaneous quantification of autoAb plus total PSA was achieved in one reaction, and termed the "A+PSA" assay., Results: Peptide epitopes from the above 6 PCAA were identified and confirmed that autoAb against these peptide epitopes reacted specifically with the full-length protein. A pilot study was conducted with the A+PSA assay using pre-surgery sera from 131 biopsy-confirmed prostate cancer patients and 121 benign prostatic hyperplasia and/or prostatitis patients. A logistic regression-based A+PSA index was found to enhance sensitivities and specificities over PSA alone in distinguishing prostate cancer from nonmalignant cases. The A+PSA index also reduced false positive rate and improved the area under a receiver operating characteristic curve., Conclusions: The A+PSA assay represents a novel platform that integrates autoAb signatures with a conventional cancer biomarker, which may aid in the diagnosis and prognosis of prostate cancer and others.

We investigated whether the improvement of lower urinary tract symptoms (LUTS) and urinary adenosine triphosphate (ATP) level were related. Fifty-seven patients and 13 normal controls were enrolled in this study. All of the male patients had benign prostatic hyperplasia (BPH), and all of the female patients had overactive bladder (OAB). We administered an alpha-1 adrenergic receptor antagonist (tamsulosin hydrochloride) for BPH, while OAB patients received an anti-muscarinic agent (propiverine hydrochloride). Before and after treatment, we examined LUTS and urinary ATP/creatinine ratio. The urinary ATP/creatinine ratio was lower in males than females in both controls and patients. In the BPH patients, administration of the alpha-1 receptor antagonist decreased LUTS and urinary ATP/creatinine ratio, and improvement of LUTS was greater in patients with a high baseline urinary ATP level. In the OAB patients, administration of the anti-muscarinic agent decreased LUTS and urinary ATP/creatinine ratio, and improvement of LUTS was greater in patients with a high baseline urinary ATP level. Improvement of LUTS by treatment with the alpha-1 receptor antagonist or the anti-muscarinic agent was related to the decrease of urinary ATP/creatinine ratio in patients with BPH or OAB. Measurement of urinary ATP can be used as a marker of pathologic bladder function.

Purpose: Carbonic anhydrase 9 (CA9) is the most promising molecular marker described for renal cell carcinoma (RCC) to date. We investigated whether transduction of monocytes from peripheral blood with adenovirus encoding the CA9 gene (AdV-CA9) could stimulate a T-cell mediated immune response against cancer cells expressing CA9. The ability to consistently generate a T-cell response is an important step toward the development of a CA9-specific RCC vaccine., Experimental Design: AdV-CA9 was generated using the AdEasy system. AdV-CA9-transduced peripheral blood mononuclear cell (PBMC)-derived monocytes were used to raise CTLs from autologous peripheral blood lymphocytes (PBLs). The ability of CTLs to lyse targets expressing CA9 was assessed by (51)Cr-release., Results: Monocytes were efficiently transduced with AdV-CA9. In five of six experiments, AdV-CA9-transduced monocytes were able to induce a population of CTLs from bulk PBLs. CTLs were capable of lysing autologous, but not allogeneic monocytes expressing CA9. Furthermore, CTLs were able to lyse autologous RCC tumor cells expressing CA9. The ability of CTLs to lyse relevant targets was blocked by anti-CD3, anti-CD8, and anti-MHC class I antibodies demonstrating a MHC class I restricted response., Conclusions: These results suggest that PBMC-derived monocytes transduced with AdV-CA9 can generate RCC-specific MHC class I restricted CTLs capable of lysing CA9-expressing cancer cells. Transduction of PBMC-derived monocytes with adenovirus provides a simple and effective alternative to the use of dendritic cells for the induction of antigen-specific CTL.

Aim: Many patients with stress urinary incontinence do not have enough motivation to continue pelvic floor muscle training (PFMT) by themselves. Therefore, a device was created to support PFMT, and its effect was examined., Methods: Forty-six women with stress urinary incontinence were assigned to a control group or a device group in order of presentation. A pamphlet on PFMT was given to control patients, while the same pamphlet plus the device and instructions on its use were given to patients in the device group. The device had a chime that was set to sound three times a day when exercise sessions were scheduled. PFMT consisted of fast and slow pelvic floor muscle contraction exercises that were performed for 2 min and followed a rhythm set by the device., Results: After 8 weeks, 20 patients from the control group and 21 patients from the device group could be evaluated. In the control group, only the quality of life (QOL) index improved significantly. In the device group, however, the daily number of incontinence episodes, the number of pads used daily, the QOL index, and the pad weight in the pad test improved significantly. Patients in the device group said that they felt obligated to perform PFMT when the chime sounded. Forty-eight percent of patients from the device group were satisfied with the outcome of PFMT, while only 15% were satisfied in the control group., Conclusion: This device may be useful to support the management of stress urinary incontinence.

Purpose: We investigated the ability of the fusion protein granulocyte-macrophage colony-stimulating factor and carbonic anhydrase IX (GMCA-9)(1) to induce an immune response in vitro and in vivo for the development of a GMCA-9-based kidney cancer vaccine., Experimental Design: Human dendritic cells (DCs) were transduced with a recombinant adenovirus containing the GMCA-9 gene and tested for their capacity to induce CA9-specific cytotoxic T lymphocytes in vitro. Tumor growth was studied in severe compromised immunodeficiency disease (SCID) mice s.c. injected with R11-GMCA-9, a human renal cell carcinoma cell line stably transfected with the GMCA-9 gene. Involvement of natural killer (NK) cells in the antitumor activity of GMCA-9 was determined in SCID mice treated with the NK-blocking agent anti-asialoGM-1., Results: DC and R11 cells transduced with GMCA-9 produced a GMCA-9 protein that is targeted to the cell membrane and partially processed to granulocyte macrophage colony-stimulating factor- and CA9-like products. Furthermore, GMCA-9 was capable of inducing DC maturation, as well as CA9-specific cytotoxic lymphocytes in vitro. Tumor growth of R11 cells in SCID mice was significantly inhibited after transfection with the GMCA-9 fusion gene (P < 0.01). In mice treated with anti-asialoGM-1, R11-GMCA-9 tumors grew significantly faster than those of control mice (P < 0.05), suggesting an involvement of NK cells., Conclusions: Our results suggest that the fusion protein GMCA-9 is capable of generating an immune response both in vitro and in vivo. Additional studies will confirm the utility of ex vivo GMCA-9-transduced DCs as a kidney cancer vaccine.

Purpose: Upper pole tumors with direct extension into the adrenal gland are currently staged as pT3a tumors in the 1997 TNM staging system. To determine whether the clinical behavior of pT3a adrenal tumors differs from that of tumors with perinephric fat invasion (also stage pT3a) a retrospective analysis was performed., Materials and Methods: Of 1,087 patients who underwent nephrectomy 27 were identified with direct adrenal involvement and 187 were identified with perinephric fat or renal sinus involvement. Variables and outcomes analyzed in each group included the percent of patients with metastatic disease at presentation, lymph node involvement, Eastern Cooperative Oncology Group score, response to immunotherapy, and median and overall survival using Kaplan-Meier curves., Results: Median survival for patients with pT3a disease and perinephric or renal sinus fat involvement was 36 months with a 36% 5-year cancer specific survival rate. In contrast, patients with adrenal gland invasion had significantly worse survival at a median of 12.5 months and a 0% 5-year cancer specific survival rate (p <0.001), which was similar to median survival of those with stage pT4 disease (11 months)., Conclusions: Upper pole tumors with direct extension into the adrenal gland predict significantly worse survival than similarly staged tumors with fat invasion and they have a prognosis similar to that of stage pT4 disease. While these data await external validation, consideration should be given to re-categorizing tumors with direct adrenal gland involvement as stage pT4 or in a subcategory such as pT4a.

Purpose: In this study, we studied the immune response against to human renal cell carcinoma and its antigensity., Methods: Mixed lymphocyte tumor culture test was performed using tumor cells as stimulator cells, peripheral blood lymphocytes from tumor patient (autologous) or healthy volunteer (allogeneic) as responder cells, and tumor cells or peripheral blood lymphocytes from tumor patient as target cells. The cytotoxic activity of mixed lymphocyte tumor culture test was assayed by 51Cr-relase test, and cell surface antigens presented on tumor cells or peripheral blood lymphocytes were assayed by antibody block test., Results: The cytotoxic activity against to tumor cells was induced from allogeneic peripheral blood lymphocytes by mixed lymphocyte tumor culture test. Its cytotoxic activity was inhibited by anti-CD8 antibody treatment of peripheral blood lymphocytes and anti-HLA class II antibody treatment of tumor cells. Furthermore, allogeneic peripheral blood lymphocytes induced to tumor cells did not damage peripheral blood lymphocyte of the tumor patient derivation., Conclusion: Renal cell carcinoma may express tumor specific antigen restricted to HLA class II antigens that could be recognized by allogeneic CD8 positive T lymphocytes.

A total of 163 patients with localized prostate cancer underwent retropubic radical prostatectomy and pelvic lymphadenectomy at a single hospital from 1989 to 1998. We reviewed the patients in terms of their prognostic factors and survival. The patients without advanced diseases were diagnosed as having prostate carcinoma, using either biopsies or transurethral resection of the prostate. The carcinomas were categorized into localized prostate carcinomas (stage A, B or C) as a result of digital rectal examinations, computed tomography scans and bone scans. The patients were informed of the risk of surgery and, if they agreed to sign the consent form, underwent radical prostatectomy under general and epidural anesthesia usually 2 months after a positive biopsy. The surgical specimens were sent for pathology and were graded according to classifications of well-, moderately and poorly differentiated adenocarcinoma. The patients were usually discharged from the hospital 2-3 weeks postoperatively and had regular follow-up treatment. The mean age (+/- SD) was 68.75 (+/- 5.59) years and the mean follow-up period was 47.2 months. There was a significant difference (34.4%) in pathologic grades between biopsy and surgical specimen. In a quarter of the patients (approximately 26.4%) upgrading of the surgical report occurred despite neoadjuvant therapy. Three-year, 5-year and 7-year actuarial survival rates were 91.8%, 79.9% and 71.9%, respectively. Patients with organ-confined prostate cancer underwent radical prostatectomy and survived a fairly good period of time. Histologic upgrading was frequently observed within a short period of time (2 months).

We report a case of vesicorectal fistula caused by a pelvic foreign body. An 84-year-old woman presented with urinary tract infection and bladder stone. During transurethral lithotripsy, a foreign body was observed in the stone. CT and colonoscopy revealed a vesicorectal fistula due to a foreign body. After continuous bladder washout over a period of one month, resection of the foreign body, fistulectomy, and sigmoidostomy were performed. The foreign body was suspected to be a medical mesh from a sling operation. After the surgery, the patient's course was uneventful. This is the second patient with vesicointestinal fistula due to a foreign body in the Japanese literature.

A 12-year-old boy presented to the Naha Municipal Hospital complaining of back pain. After intravenous pyelography, computed tomography, magnetic resonance imaging, ultrasonography and biopsy, he was suspected to have sarcoma of the prostate and was referred to the University of the Ryukyus Hospital. Acute renal failure of the post renal type was evident, accompanied by minimal hydronephrosis. Emergency hemodialysis and right ureterostomy were performed, as was a transurethral prostate biopsy. The specimen showed a poorly differentiated sarcoma not otherwise classifiable. After recovery from surgery, chemotherapy was attempted over 2 months, but the patient died of tumor 250 days after admission.

Two patients, one with and one without a history of nephrectomy for renal cell carcinoma, presented with lower abdominal pain. One of them, a 49-year-old man, had tumors in the right kidney and the right ischiadic bone. He underwent nephrectomy and pathologic findings showed renal cell carcinoma (tubular type, granular cell subtype, INF-gamma, G2). The other patient, a 33-year-old man with a previous history of left nephrectomy for renal cell carcinoma (tubular type, granular cell subtype, INF-alpha, G2), was found to have a large tumor in the pelvis, extending from the pubic and iliac bones to the hip joint. Both patients underwent embolization of the hypervascular mass using a vascular coil followed by hemipelvectomy under general anesthesia. The pathology reports confirmed bone metastases from renal cell carcinoma. Both patients survived surgery and their postoperative courses were uneventful without urinary or bowel incontinence. However, impaired potency was noted in the latter case. Immunotherapy with INF-alpha was resumed immediately after surgery.

Objective: Bladder neck hypermobility causes cystocele in middle to old elderly women. We developed an easy and useful surgical technique for cystocele., Methods: Thirteen patients with cystocele (grade 2-4) were operated by fornix of the vagina suspension. Patients were placed on lithotomy position under general or spinal anesthesia. Lower midline or lower abdominal transverse incision was made to open the peritoneum and denuded vesicouterine pouch. Several nylon sutures were placed on the lateral side of exposed fornix of the vagina. These sutures were suspended to anterior layer of the rectus sheath. Fornix of the vagina was fixed to the rectus muscle, so the prolapsed bladder wall was pulled up in normal position., Results: Operating time ranged from 15-110 minutes (average 73 minutes). Ten patients of thirteen were successful up to 2-43 months postoperatively. Cystocele recurred in three patients of thirteen. Two patients was re-operated by the same method, but one of them recurred. Two of three recurrent patients had grade 4 cystocele., Conclusion: Fornix of the vagina suspension for cystocele seems useful and promising because of easy procedure without serious morbidity, especially in elderly high-risk patients.

We report 3 cases of hypogonadotropic hypogonadism and the effects of human chorionic gonadotropin (HCG) monotherapy on plasma testosterone levels, which were related to clinical results. The patients were males 29, 21 and 14 years old. Each received 5,000 units of HCG subcutaneously or intramuscularly twice or three times a week for 16 to 40 months. Genital effects, including an increase in testicular volume were seen in all patients after 2 or 3 months. The increase in plasma testosterone level after HCG therapy was significantly correlated with the genital effects similarly to other treatments. Moreover, spermatozoa appeared in one case.

Between 1988 and 1996, we treated five patients with primary carcinoma of the female urethra between 65 and 79 years of age. Presenting symptoms included a urethral mass in 2 patients, hematuria in 1, dysuria in 1 and urethral bleeding in 1. Histopathology revealed squamous cell carcinoma in 4 cases and transitional cell carcinoma in 1. Clinical stage according to Grabstald's classification comprised Stage A in two cases, Stages B, C and D in one each. The modes of treatment were surgical resection alone in two, radiation therapy alone in two, and surgery with adjuvant chemotherapy in one case. Three patients without disease and two with disease are olive from 5 to 87 months after diagnosis.

Thy.1lowCD3- cells obtained from nylon wool-passed murine bone marrow (NW-BM) cells by cell sorting did not express CD4, CD8, or T cell receptor-alpha/beta and -gamma/delta on their cell surfaces. An extremely limited number of B10.BR (H-2k) responder lymph node (LN) cells were stimulated with B10.D2 (H-2d) stimulator spleen cells in cultures containing the minimum required dose of rat T cell growth factor (TCGF). In these cultures, the generation of cytotoxic T lymphocytes (CTL) was very low. B10.BR Thy.1lowCD3- NW-BM cells, added to these cultures, could augment the CTL generation vigorously, but neither B10 (H-2b) nor B10.D2 cells could. When B10 LN cells were used as responder cells in these cultures, B10 Thy.1lowCD3- NW-BM cells could augment the CTL generation, but neither B10.BR nor B10.D2 cells could. Similar findings were obtained when Lyt-2+ cells or Thy.1+L3T4- (CTL precursor) cells sorted from spleen cells were used as responder cells. Both elements, rat-TCGF and Thy.1low CD3- NW-BM cells, were essential for this augmentation of the CTL generation in this culture system because neither one alone could augment generation, and rat-TCGF could be replaced by Thy.1+ Lyt-2- helper T (Th) cells sorted from spleen cells. These findings showed that NW-BM cells could augment CTL precursors in a self-major histocompatibility complex (self-MHC)-antigen restricted manner, and further that both NW-BM cells and Th cells had different and independent functions to induce CTL.