Search

We report the results of a retrospective analysis in 27 pediatric patients who received low-dose MTX as the second-line treatment for steroid-refractory or -dependent acute and chronic GVHD. Between July 2000 and May 2006, 10 patients with aGVHD and 17 with cGVHD were treated with MTX at a dose of 3-10 mg/m(2) weekly. Seven of ten patients (70%) with aGVHD responded well to MTX, thus resulting in the achievement of either a complete response (CR) or a partial response (PR). The dose of prednisone could be reduced to equal to or lower than 1 mg/kg in the responding patients at the end of MTX therapy. The median number of MTX administrations was five (range, 1-7). Ten (58.8%) of seventeen patients with cGVHD achieved CR or PR. The dose of prednisone could be reduced to lower than 0.4 mg/kg in 16 of 17 patients and seven patients could discontinue prednisone. The median duration of MTX administration was 18 months (range, 1-68). The toxicities of grade III to IV occurred in only six patients presenting cytopenias or elevated levels of serum transaminases. Low-dose MTX was tolerable and effective for the steroid-refractory or -dependent GVHD in reducing the dose of steroid without increasing the risk of opportunistic infection.

Cyclopterids were hatched from egg batches that were laid in two empty buccinid snail shells collected from a depth of 340 m in the Sea of Japan. Larvae were reared to identify species and to describe the morphological changes associated with metamorphosis. The fin rays of all fins were mostly complete and the pelvic fins were modified to form suckers, or adhesive discs, at the time of hatching. Juveniles immediately attached themselves to the bottom and there was no planktonic stage. The body surface was smooth with no spines or bony tubercles. At 4 months after hatching, the fine spines present on the head and trunk of juveniles transformed into bony tubercles. At 7 months after hatching, fishes became sexually dimorphic including the position and development patterns of bony tubercles. Importantly, these sexually dimorphic changes in morphology corresponded closely with descriptions of different species. Specifically, females could be classified as Eumicrotremus asperrimus, and young and fully developed males as Cyclopteropsis bergi and Cyclopteropsis lindbergi, respectively. These observations resolved a previously ambiguous hypothesis regarding the taxonomy of these cyclopterid taxa. Cyclopteropsis bergi and C. lindbergi may be synonyms of E. asperrimus.

Bosentan is an oral dual endothelin receptor antagonist, which has been shown to be efficacious for preventing new digital ulcers in patients with systemic sclerosis (SSc) in two high-quality randomized controlled trials. However, its efficacy for nondigital ulcers in SSc remains unknown.To evaluate the efficacy of bosentan on nondigital ulcers in patients with SSc.Bosentan was administered to five patients with SSc with pulmonary arterial hypertension, who also had nondigital ulcers refractory to conventional treatments. The efficacy of bosentan on nondigital ulcers and its association with clinical features of ulcers were analysed.The nondigital ulcers refractory to conventional treatments were significantly improved by the administration of bosentan in cases surrounded with severe cyanosis. In contrast, nondigital ulcers without cyanosis were still refractory to bosentan therapy.Bosentan may be efficacious for accelerating the healing of nondigital ulcers with severe cyanosis, suggesting that nondigital ulcers caused by severely impaired peripheral circulation are highly responsive to this treatment.

Aggravation of anemia in chronic renal failure patients by angiotensin-converting enzyme inhibitors (ACEIs) has been attributed to the inhibition of angiotensin II which facilitates erythropoietin(Epo) production. This study was aimed at evaluating whether ACEIs aggravate anemia in maintenance hemodialysis patients and to investigate the influence of ACE gene polymorphism on erythropoiesis in these patients. Ninety-one hemodialysis patients were divided into 2 groups, based on whether or not they were administered ACEIs, into the ACEI group(n = 24) and the non-ACEI group(n = 67), and comparisons were made of the doses of recombinant human Epo(rHuEpo) administered, the hematocrit(Hct) and the plasma Epo concentrations. Among the patients in the non-ACEI group, only 17 did not receive rHuEpo, while all of the patients in the ACEI group received rHuEpo. The average dose of rHuEpo was 102.7 +/- 45.4 IU/kg/week in the ACEI group and 57.8 +/- 55 IU/kg/week in the non-ACEI group and the difference between the two groups was statistically significant. A statistically significant difference in the Hct was also observed between the two groups: the mean Hct in the ACEI group was 28.7 +/- 2.9% while that in the non-ACEI group was 31.1 +/- 3.7%. The plasma Epo concentrations were significantly lower in the ACEI group than in the non-ACEI group. No significant differences in the rHuEpo dose and Hct were observed between the three ACE genotype classes in either the ACEI or the non-ACEI group, however, there was a significant difference among the three genotypes in the non-ACEI group in regard to the plasma Epo concentrations; patients with the DD genotype had higher concentrations than those with the DI or II genotypes. These data suggest that anemia in maintenance hemodialysis patients is worsened by ACEIs as a result of the suppression of Epo production. Although it has been suggested that the endogenous Epo concentrations in maintenance hemodialysis patients are associated with ACE gene polymorphism, no significant influence of the ACE genotype on the rHuEpo dose or Hct was evident. Therefore, it is possible that exacerbation of anemia by ACEIs in the patients receiving rHuEpo is a result of an inhibited bone marrow response to Epo.

In an attempt to reveal a correlation between the degree of glomerular hypertrophy, interstitial damage, and hemodynamic parameters in chronic nephritis, the glomerular area (GA) and proportion of interstitial area (IA%) were determined quantitatively with an image analyzer, and the effective renal plasma flow (ERPF) and filtration fraction (FF) were determined simultaneously. The subjects were 12 patients with focal glomerulosclerosis (FGS) and 12 patients with IgA nephropathy (IgAN), all of whom had a similar glomerular filtration rate (GFR). The GFR was 58.6 +/- 11.4 ml/min/1.48 m2 in the FGS group and 53.9 +/- 13.1 ml/min/1.48 m2 in the IgAN group, and the difference between the two groups was not significant. On the other hand, ERPF was significantly lower and FF was significantly higher in the FGS group than in the IgAN group. GA was significantly higher in the FGS group than in the control group (10 kidney donors), and GA in the IgAN group was equivalent to that in the control group. IA% was almost equal in the FGS and IgAN groups, and significantly higher in both groups than in the control group. Although GA was not correlated with GFR in the two groups, it tended to be positively correlated with FF in the FGS group, and the correlation between GA and FF reached statistical significance when the IgAN group was combined with the FGS group. The above findings suggest that the pattern of progression of the glomeruli and interstitial lesions and of the intrarenal hemodynamics involved in them may differ in the FGS and IgAN groups. However, since ERPF significantly decreased in the FGS group, even though IA% was the same in both groups, the possibility that ERPF was functionally decreased in the FGS group cannot be ruled out.

The purpose of the study is to validate the split-dose method corrected with dose ratio of 99mTc-ECD for brain perfusion scan. A dose of 600 MBq of 99mTc-ECD was divided into two with various dose ratios from 1:1 to 1:4, and injected to eleven patients with various cerebral diseases. A lesser dose of 99mTc-ECD was injected under a control state for the first SPECT scan, and 15 min SPECT scan was performed 10 min after injection with a triple-head high resolution gamma camera. After the scan, the other dose of 99mTc-ECD was injected under the same control state and the second SPECT scan was performed as same as above. A ratio of the activity of the first scan to the net activity of the second scan corrected by dose ratio, defined as K, was measured in brain regions of each subject. Expected value of K was 1, but the value was distributed with large variations in each subject. The mean % error of the K value was 10.4 +/- 4.9%. Hence it is considered that activity changes by more than 20% from the control values should be required to detect a significant rCBF change in an activation SPECT study. Then, we proposed a new method in which the activity of both two SPECT scans was normalized by cerebellar or occipital activity and compared. The ratio obtained by the proposed method came closer to 1 with less variations and with less mean % error in comparison with those of K value obtained by the dose-correction method. Although the proposed method has a limitation in the use of an activation study loaded with Diamox, it may be useful to evaluate an alteration of rCBF in the study such as postural testing or finger-moving test.

The purpose of this study was to comparatively evaluate the quality of SPECT images for the mapping of rCBF using three tracers, 123I-IMP, 99mTc-HMPAO and 99mTc-ECD. We performed three SPECT studies on seven patients with various cerebral diseases under the same conditions. An effect of Lassen's correction on SPECT images obtained by HMPAO was also evaluated. The same irregular regions of interest were placed on the four transaxial SPECT images. To quantitatively evaluate the pattern of tracer uptake and image contrast, the uptake ratio, regional count/mean count of the cerebrum, and its coefficient variations (CV) were defined, respectively. The order of the value of CV was HMPAO with correctionIMPECDHMPAO without correction. HMPAO with correction showed the best image contrast, but HMPAO without correction was the worst. Uptake ratios of ECD and HMPAO with correction were decreased in the brain stem and thalamus in comparison with those of IMP. Both uptake ratios of ECD and HMPAO without correction were increased in the occipital cortex. IMP provides high quality SPECT images. Images obtained by HMPAO should be modified by Lassen's correction to increase image contrast. ECD or HMPAO should not be used to evaluate patients with spinocerebellar degeneration.

To measure distribution volume of 123I-IMP with one-point sampling of arterial blood and 2 times SPECT scans using the Magic square method (Rate constant square method), we introduced a program on a SPECT computer system. In this program four functional images; distribution volume, CBF (K1), k2 and delayed/early ratio, and absolute values with S.D. are obtained on the computer. We have been using the program on daily SPECT studies. In this study we discussed the usefulness of the method. Redistribution phenomenon of 123I-IMP, which is not exactly enough investigated, can be transformed into a functional parameter, distribution volume. Since distribution volume represents an extent of retention of 123I-IMP in brain tissue, it can play an important role to evaluate functional activity in the brain and to diagnose cerebral diseases.

The chromosomal translocation involving 3q27 is often detected in human B-cell lymphomas, especially diffuse lymphomas with a large-cell component. The BCL6 gene has been isolated from the chromosomal breakpoint in these lymphomas. Here we cloned the murine BCL6 (mBCL6) cDNA from the muscle cDNA library using the human BCL6 (hBCL6) cDNA as a probe. The predicted amino acid sequence was 95% identical to that of hBCL6. It contains six repeats of the Krüppel-like zinc-finger motif that are completely identical to those of hBCL6, indicating that the BCL6 gene is well conserved between humans and mice. Expression of the mBCL6 gene was ubiquitously detected in adult mouse tissues including lymphatic organs. Furthermore, it was induced in lymphocytes activated with phorbol ester and Ca2+ ionophore within 30 min after stimulation. This induction was not inhibited by treatment of the cells with a protein synthesis inhibitor, cycloheximide. These results suggest that BCL6 plays a role in activated lymphocytes as an immediate early gene.

Regional cerebral blood flow (rCBF) was measured in 13 patients with various cerebral disease by N-isopropyl-p-[123I]iodoamphetamine (IMP) SPECT with the microsphere model (rCBF (CbST)), which was compared with 133Xe inhalation SPECT (rCBFXe). Continuous withdrawal of arterial blood was performed for 5 minutes and SPECT image was obtained from 25 min to 55 min after the tracer injection. The reconstructed counts at 5 min was corrected using entire cerebral counts collected at 5 min, 20 min, and 60 min after the tracer injection. As compared with rCBFXe, rCBF (CbST) was underestimated in high flow areas and overestimated in low flow areas. Regional CBF was also measured using one minute short time SPECT images at 5 min (rCBF (Cb5)), 20 min (rCBF (Cb20)), and 60 min (rCBF (Cb60)) after the injection. Regional CBF tended to be underestimated with time from the tracer injection due to the wash-out from brain tissue to blood. In comparison with rCBF (Cb5), rCBF (CbST) was underestimated in high flow areas and overestimated in low flow areas. This error was considered to be due to the correction of reconstruct counts using entire cerebral counts, because of the kinetic behavior of 123I-IMP was different in each region of the brain.

We developed a new graphic method using N-isopropyl-p-[123I]iodoamphetamine (IMP) and SPECT of the brain, the graph on which all three parameters, cerebral blood flow, distribution volume (Vd) and delayed count to early count ratio (Delayed/Early ratio), were able to be evaluated simultaneously. The kinetics of 123I-IMP in the brain was analyzed by a 2-compartment model, and a standard input function was prepared by averaging the time activity curves of 123I-IMP in arterial blood on 6 patients with small cerebral infarction etc. including 2 normal controls. Being applied this method to the differential diagnosis between Parkinson's disease and progressive supranuclear palsy, we were able to differentiate both with a glance, because the distribution volume of the frontal lobe significantly decreased in Parkinson's disease (Mean +/- SD; 26 +/- 6 ml/g). This method was clinically useful. We think that the distribution volume of 123I-IMP may reflect its retention mechanism in the brain, and the values are related to amine, especially to dopamine receptors and its metabolism.

A 40-year-old woman suffered from toxemia of pregnancy in 1977 and was admitted to hospital. Thereafter, she developed nephrotic syndrome, underwent a renal biopsy, and a diagnosis of membranoproliferative glomerulonephritis (MPGN) was made. She received steroid therapy, immunosuppressive drug and anticoagulant therapy, and recovered sufficiently to be discharged from hospital in April, 1979. During subsequent ambulatory treatment at our outpatient department, her renal function deteriorated gradually, and maintenance hemodialysis was started from June, 1990. In July, 1991, she was admitted to our hospital with pleurisy and pericarditis. There was no improvement despite antibiotic treatments. Laboratory data revealed leukopenia and lymphopenia. Under suspicion of systemic lupus erythematosus (SLE), relevant tests were carried out. Immunological abnormalities such as positive LE cells and the presence of various autoantibodies, together with clinical signs of hypersensitivity to sunlight, stomatitis and serositis, satisfied the diagnostic criteria of the ARA and a diagnosis of SLE was made. This case did not exhibit any clinical or serological abnormalities except for the renal disorder for a 10-year period after the histological diagnosis of MPGN, but was eventually diagnosed as SLE as a result of the manifestation of SLE symptoms for the first time after one year of maintenance hemodialysis. Immunological abnormalities and SLE during maintenance hemodialysis are discussed in relation to other reports.

A 54-year-old woman with malignant rheumatoid arthritis was admitted with acute congestive heart failure and pulmonary hypertension. The precipitating antibody to nuclear ribonucleoprotein (nRNP) was highly positive. Her hands and feet showed typical rheumatoid deformities and Raynaud's phenomenon. In a few days her feet became to necrosis due to vasculitis. "Pulse" methylprednisolone and prednisone therapy resulted in normalization of seropositivity, and left ventricular ejection fraction with symptoms of congestive heart failure, and the elimination of ECG abnormalities. Recognition of symptoms of left ventricular dysfunction in patients with rheumatoid arthritis should prompt testing for active arteritis and/or myocarditis, because dramatic improvement may result from immunosuppressive therapy.

Urea kinetic modeling (UKM) was carried out to evaluate the water control in patients undergoing long-term hemodialysis. In 21 patients on chronic dialysis, the results of two different determinations of the total body water, i.e. by the deuterium oxide (D2O) method and by UKM, were compared. A correlation was observed with Y = 0.98X + 5.9 (P less than 0.01, r = 0.91) for males and Y = 0.97X + 6.2 (P less than 0.01, r = 0.90) for females, indicating that UKM is useful for determining the total body water. In addition, the 21 patients were classified into two groups based on their ECG findings, and UKM was performed in the two groups for comparison. The values of the total body water were 68.5 +/- 4.0% and 68.6 +/- 6.2% of body weight, respectively, with no significant difference between them. However, the CTR was 50.2 +/- 2.8% and 46.2 +/- 4.4%, respectively. Thus, not only X-ray examinations but also UKM should be carried out to determine the standard weight (SW-DW) in the presence of cardiac dysfunction. Instructions for water control were given when the total body water exceeded 73% during the UKM measurements over 5 years, which allowed an optimal total body water to be maintained thereafter. The possible influence of erythropoietin (EPO) was also examined by performing UKM in 8 cases receiving EPO and 7 cases without EPO. No noticeable difference was observed between the two groups. 17 patients using a polyacrylonitrile (PAN) membrane were further divided into those with and those without EPO to evaluate the possible influence of the PAN membrane-EPO combination. As a result, no significant difference was demonstrated, suggesting that UKM can be satisfactorily performed under such conditions. In 11 patients on chronic dialysis, the levels of alpha-human atrial natriuretic peptide (alpha-hANP) were measured pre- and post-dialysis to examine the relationship between the change in alpha-hANP and rate of weight loss (%). A significant correlation was observed with Y = 12.8X + 5.1 (P less than 0.05, r = 0.68). In conclusion, UKM was found to be useful for evaluating the water control and for assessing the optimal dialysis in patients receiving long-term hemodialysis.

The pharmacokinetics and optimum dose for maintenance of disopyramide (DP) which is effective against arrhythmia were studied in patients with chronic renal failure (CRF, n = 10), who had a creatinine clearance (Ccr) less than 30 ml/min. The plasma concentrations (PC) of DP and mono-isopropyl-disopyramide (MDP) an active metabolite of DP, were measured by high performance liquid chromatography. Samples from patients and controls were obtained at 0, 1, 2, 3, 4, 6, 8, 12, 24, 33, and 48 hr after oral administration (OA) of 100 mg DP. The pharmacokinetic parameters were calculated using a two-compartment model. In CRF, the plasma half life (T 1/2) of DP was 5.25 to 22.42 hr (average is 12.45 hr) and that of MDP was 5.09 to 131.66 hr (average is 16.9 hr). In normal controls, the T 1/2 of DP was 6.05 hr, but that of MDP could not be determined the available sensitivity of measurement. T max was 3.11 hr at the total PC of DP and MDP, and C max was 2.48 g/ml on average. In conclusion, the present study revealed that: (1) the PC of a mixture of DP and MDP should rise following OA of DP every 8 or 12 hr in CRF; (2) it is necessary therefore to monitor the accumulation of MDP after rolling OA of DP; and (3) OA of DP every 24 hr can maintain an effective PC.

The effects of CaCO3 with vitamin D metabolite and without vitamin D metabolite on secondary hyperparathyroidism were investigated in 18 patients undergoing maintenance hemodialysis. 9 patients (Group 1) were treated with 1 microgram/day 1 alpha (OH)D3 and 2 g/day Al(OH)3, and the other 9 patients (Group 2) received 2 g/day Al(OH)3 without vitamin D metabolite. CaCO3 at amounts of 3 g/day was subsequently administered to all patients instead of Al(OH)3. The levels of mid portion-parathyroid hormone (M-PTH) in Group 2 and of 1,25-dihydroxyvitamin D3 in Group 1 during the baseline period were significantly increased as compared to those in the other group, respectively. In Group 1 only, the level of serum ionized calcium was appreciably elevated at the 4th and 12th weeks as compared to the baseline value, and the level of M-PTH was significantly decreased at the 4th and 12th weeks as compared to the baseline value. The levels of serum phosphate, calcitonin, magnesium and bicarbonate in both groups at the 4th and 12th weeks were not appreciably different from the baseline values. The level of serum aluminum in all patients of both groups were reduced at the 12th week as compared to the baseline values. A close correlation was recognized between M-PTH and the level of intact parathyroid hormone. It is concluded that prescription of 3g/day CaCO3, together with adequate doses of vitamin D metabolite, can ameliorate mild secondary hyperparathyroidism.

C3 nephritic factor (C3 NeF) has been found mainly in the sera of patients with membranoproliferative glomerulonephritis (MPGN) and partial lipodystrophy (PLD). We examined whether peripheral blood mononuclear cells (PBMC) from patients with PLD and MPGN could produce C3 NeF. We investigated the in vitro immunoglobulin synthesis of PBMC with mitogen. We further studied whether or not C3 NeF was included in the IgG of the culture supernatants by the C3bBb stabilizing activity and agglutination assay. The IgG of PLD patient was able to agglutinate only EAC4bBb cells and none of the other intermediate cells. We thus demonstrated that C3 NeF could be produced in vitro by PBMC derived from the patient with PLD. However, as regard case of C3 NeF weakly positive and C3 NeF negative patients, C3 NeF couldn't be produced in vitro by PBMC derived from the patients.

The relationship between red blood cell sorbitol content and diabetic complications (cataract, retinopathy, neuropathy, and nephropathy) was examined in 23 non-insulin-dependent diabetic (NIDD) patients. Sorbitol content was abnormally high in 21 cases out of 23 NIDD patients. Sorbitol content in the non-neuropathy group and neuropathy group was 47.3 +/- 11.9 and 59.6 +/- 23.6 nmol/gHb, respectively. In the non-cataract group and cataract group, it was 49.0 +/- 17.6 and 66.0 +/- 23.5 nmol/gHb, respectively. The contents in the Scott I group and Scott II + III group were 54.9 +/- 20.7 and 58.7 +/- 24.0 nmol/gHb, respectively. Sorbitol content in the non-nephropathy group and nephropathy group was 52.8 +/- 19.8 and 61.1 +/- 21.9 nmol/gHb, respectively. The possibility that glyceraldehyde reductase (GAR) and sorbitol dehydrogenase (SDH) levels in red blood cells are also useful indicators of the presence of diabetic complications is strongly suggested.

Four patients with mitral valve prolapse and ventricular tachycardia or fibrillation were described. Case 1 was a 46-year-old man with syncope due to ventricular fibrillation. Case 2 was a 36-year-old woman with palpitation and dizziness due to ventricular tachycardia. Case 3 was a 47-year-old man with palpitation and dizziness due to ventricular tachycardia. Case 4 was a 38-year-old man with syncope due to torsade de pointes. Left ventriculograms showed mitral valve prolapse in all cases. Coronary arteriograms were also normal, supporting a noncoronary etiology of the arrhythmia. Patients with unexplained ventricular arrhythmias should be screened for mitral valve prolapse.

The T-colony-forming capacity was examined in 13 normal subjects and 14 patients with biopsy-proven lipoid nephrosis (LN). Eighteen additional patients with other well-defined forms of glomerulonephritis were studied as a disease control. Significantly fewer T lymphocyte colonies were found in LN patients and the nephrotic syndrome (NS) than in normal controls. A similar change could be observed in the groups with other types of NS. LN patients with NS had the lowest values of T-colony-forming cells (TCFC), but there was no statistically significant difference between the groups of nephrotic subjects. It was also of interest that peripheral blood lymphocytes (PBL) from 3 patients with lupus nephritis (SLE) produced significantly low levels of TCFC. The lower levels of TCFC in LN could be enhanced when exogenous interleukin 2 (IL 2) was added to the system. We also examined the production of T-colony-stimulating factor (TCSF). The TCSF production by stimulated PBL from LN patients was lower than in normal subjects. To explain our observations, we presumed that the T colony dysfunction seen in LN patients with NS might in part be due to the decreased TCSF activity.

Both C3 nephritic factor (C3NeF) and C4 nephritic factor (C4NeF) were found in the serum of two patients with hypocomplementaemic membranoproliferative glomerulonephritis type 1 (H-MPGN type 1). Both stabilizing activities were associated with the IgG fraction. The serum levels of C3 and C5 were quite low, whereas the levels of early components and control proteins were in the normal range.

In order to reconstruct the blocked CSF pathway, we attempted to excise the Liliequist membrane in 22 patients with subarachnoid hemorrhage resulted from ruptured intracranial aneurysms. After clipping the aneurysmal neck, the Liliequist membrane was reached through the space between the optic nerve and the internal carotid artery within the same operative field. As a result, the incidence of postoperative ventricular dilatation was remarkably reduced in comparison with control cases without Liliequist membranotomy. The necessity for the shunt operation for post-SAH hydrocephalus was also reduced. On the other hand, the incidence of postoperative subdural effusion increased in the group with Liliequist membranotomy. This suggests that the blockage of the arachnoid villi is probably the cause of disturbances in CSF absorption in some cases following subarachnoid hemorrhage. In such cases, the Liliequist membranotomy may be ineffective in restoring CSF circulation following subarachnoid hemorrhage.

To determine whether patients with systemic lupus erythematosus (SLE) and active nephritis have more profound defects in cellular immune responses, we studied cell-mediated immunity (CMI) in 12 patients with lupus nephritis (LN) and 11 patients with chronic mesangial proliferative glomerulonephritis (CGN) without renal insufficiency. The LN patients had a significant depression in CMI, characterized by impaired delayed hypersensitivity skin reactivity to keyhole limpet haemocyanin (KLH), decreased percentage of T cells and diminished lymphocyte transformation to phytohaemagglutinin (PHA). The levels of concanavalin A (Con A)-induced suppressor cell activity (SCA) were significantly lower in LN patients compared with those in normal controls and those in CGN patients. The levels of all CMI parameters for the 6 LN patients with the nephrotic syndrome (NS) were significantly more decreased when compared with those of the 6 LN patients without NS. In contrast, the CMI levels in CGN patients with or without NS did not differ from normal subjects. These findings may lend further insight into the understanding of the immunoregulatory defect in LN.

To determine whether patients with systemic lupus erythematosus (SLE) and active nephritis have more profound defects in cell-mediated immunity (CMI), we studied T-colony-forming cells (TCFC) in 12 patients with lupus nephritis (LN) and 14 patients with chronic mesangial proliferative glomerulonephritis (CGN) without renal insufficiency. We also examined the activity of T-colony-stimulating factor (TCSF) in media conditioned by phytohaemagglutinin (PHA) stimulated peripheral blood lymphocytes (PHA-LCM). The levels of TCFC and TCSF were decreased in patients with LN compared with those in normal controls and lower in LN patients with the nephrotic syndrome (NS) than in those without NS. In contrast, these CMI parameters in CGN patients with or without NS did not differ from normal subjects. TCSF activity for TCFC in both normal individuals and LN patients was removed from PHA-LCM with interleukin 2 (IL 2) receptor bearing cultured T cells. These in vitro findings suggest that IL 2 is the essential factor contained in PHA-LCM. Our observations may lend further insight into the understanding of the immunoregulatory defect in LN.

Antitumor activity of 1-(gamma-chloropropyl)-2-chloromethylpiperidine hydrobromide (CAP-2) was studied in vivo and in vitro, using various rat ascites hepatoma cell lines. Among eight ascites hepatoma cell lines, AH-13 was extremely sensitive both to in vivo antitumor and to in vitro lethal action of the agent, whereas AH-44 was resistant in both cases. The sensitivity of ascites hepatoma cell lines to CAP-2, nitrogen mustard N-oxide, 4-nitroquinoline 1-oxide, and ultraviolet ray in vitro was widely different but their relative sensitivities were very similar against these agents. For all the agents, AH-13 was inactivated very rapidly and AH-109A moderately, whereas AH-44 was relatively resistant. These results indicate that the sensitivity of the cells to CAP-2 may be closely related to their repair-capability of damaged DNA. Similar experiments using various DNA repair-deficient mutants of Escherichia coli B strain demonstrated that the repair-deficient mutants were several times more sensitive to CAP-2 than the wild type strain. From these results, it may be concluded that CAP-2 induces DNA lesions repairable by the same repair mechanisms that work on pyrimidine dimers.

Although mucolipidosis, a fatal metabolic storage disorder, is associated with cardiovascular abnormalities, detailed, non-invasive cardiac examinations have not been well documented. We studied 4 children with type II and type III mucolipidosis, 3 of whom had unequivocal evidence of aortic regurgitation characterized by phonocardiography and M-mode echocardiography. Two-dimensional echocardiography showed an aortic valve prolapse in 3, a mitral valve prolapse in 2 and a tricuspid valve prolapse in 1. The QT interval was prolonged in 2 cases. In 1 autopsy case, we found considerably thickened and retracted aortic, mitral, and tricuspid valves, and accumulation of the foam cells in the myocardium. Echocardiography revealed similar findings in another 3 cases. We conclude that cardiac manifestations in this disorder should be examined carefully particularly by the use of echocardiography which is an excellent technique for detecting cardiovascular abnormalities in mucolipidosis.