Lesions in lateral hypothalamic areas increase splenocyte apoptosis.

OBJECTIVE: The lateral hypothalamic area (LHa) is involved in various functions such as feeding, drinking, sexual and reward behavior, among others. Recently, we demonstrated that the LHa can regulate cellular immunity in the spleen. In experiments involving the LHa, it was noticed that the spleen shrinks noticeably after LHa destruction. To explore this phenomenon further, the effect of LHa lesioning on splenocyte apoptosis was investigated. METHODS: Male Wistar-King-Aptekman rats underwent bilateral lesioning of their LHa and consequent spleen weights, splenocyte numbers and apoptosis were measured. For the detection of splenocyte apoptosis, both ELISA, which measures DNA fragmentation within the splenocytes, and flow cytometry, which measures the percentage of apoptotic lymphocytes in the spleen, were used. RESULTS: In the LHa-lesioned rats, spleen weights and the number of splenocytes decreased significantly within 24 h. Additionally, in the spleen, lymphocyte apoptosis significantly increased compared to the control after 6 h. CONCLUSION: These results suggest that the LHa may play a role in immunoregulation by affecting lymphocytes in the spleen through apoptosis and may be relevant to the pathway of stress-induced apoptosis.

Synthesis and antibacterial activity of new 1beta-methylcarbapenems having the potential for intramolecular nonbonded S...O interactions.

Mercaptoacetyliminothiadiazoline derivatives (19, 20) useful for the pendant moiety of 1beta-methylcarbapenem antibiotics were efficiently synthesized. Acetyl derivative (18) of 20 was submitted to X-ray analysis, and a significant nonbonded S...O close contact was recognized in the crystallographic structure. New 1beta-methylcarbapenems (5, 6) were synthesized by exploiting 19 and 20, and exhibited considerable antibacterial activities in vitro.

Lateral hypothalamus modulates the intrinsic splenic natural killer cell activity in rats.

Electrical stimulation of the lateral hypothalamus (LH) in rats increased splenic natural killer (NK) cell activity, whereas electrical ablation of the LH decreased it. However, the percentage of NK cells, as detected by the anti-NKR-P1 monoclonal antibody, in the spleen did not change significantly. These results suggest that the LH does not modulate the splenic NK cell activity by increasing the NK cell number but by increasing the intrinsic NK cell activity itself.

[Autoradiographic studies of oxalate distribution in rat kidney].

BACKGROUND: We performed macro and micro-autoradiographic studies using 14C-oxalate in normal and hyperoxaluric rats in order to elucidate intrarenal distribution of oxalate and to determine where calcium oxalate crystal can be adhere in the kidney. METHODS: Macro and micro-autoradiographic studies of the kidney in normal rats were carried out at intervals of 15, 30 and 90 min after intravenous administration of 14C-oxalate (37 MBq/kg BW). Hyperoxaluria was induced by vitamin B6 deficient diet. The procedure of macro and micro autoradiography is the same as that in normal rat. RESULTS: In normal rats, macroautoradiogram showed that the radioactivity of 14C-oxalate exists in the whole kidney, and microautoradiogram identified this radioactivity mainly in the extraluminal space of renal tubules at 15 min. Macro and micro-autoradiograms taken 90 min after the injection showed practically no radioactivity of 14C-oxalate in the cortex or the medulla, but it was located in the extraluminal space of the papilla. In hyperoxaluric rats, macroautoradiogram showed some spotty accumulations of 14C-oxalate in the inner medulla and papilla. Microautoradiogram revealed that these accumulations are mainly seen in the extraluminal space. CONCLUSION: These results indicate that in normal rats the injected 14C-oxalate remains in the renal papilla, especially in the extraluminal space, when nearly all oxalate was excreted by urine, and in hyperoxaluric rats 14C-oxalate exists there as calcium oxalate crystal or microlith.

Criteria for differentiation of normal and abnormal uroflowmetrograms in adult men.

OBJECTIVE: To study parameters which serve as criteria for differentiation of normal and abnormal uroflowmetrograms. SUBJECTS AND METHODS: A total of 105 subjects were investigated, 43 of whom had no symptoms of dysuria, 57 of whom had dysuria demonstrated as an abnormal uroflowmetrogram, subjective symptoms and a small residual urine volume, and five patients who were about to undergo transurethral resection of the prostate. The three parameters used to specify the shapes of the uroflowmetrogram curves were: (i) the ratio of the maximum flow rate (Qmax) and the voiding time (T100), Qmax/T100; (ii) the ratio of the time to peak flow (TQmax) and the voiding time, TQmax/T100; and (iii) the newly introduced voiding efficiency (epsilon), measured by the ratio of the voided volume (VV) and T100 x Qmax, epsilon = VV/(T100 x Qmax), were taken for each patient. RESULTS: The criteria for normal uroflowmetrograms were: Qmax/T100 > or = 0.78, 0.32 < or = TQmax/T100 < or = 0.54, 0.63 < or = epsilon < 1, respectively. In the patients who underwent transurethral resection of the prostate the values of all three parameters improved and returned almost to normal after operation. CONCLUSION: Using these three parameters the micturition pattern can be expressed quantitatively.

[A case report of ureteral stump metastasis from renal-cell carcinoma].

This is a case report of the 21st documented case of ureteral metastasis from renal cell carcinoma. A 75-year-old woman was admitted because of asymptomatic gross hematuria. Right radical nephrectomy for renal cell carcinoma had been performed 2 years and 9 months prior to admission. Cystoscopy revealed efflux of blood from right ureteral orifice. Right retrograde ureterogram revealed a filling defect at the upper end of the stump, where a soft tissue mass was observed by computerized tomographic scan. She underwent right ureteral stump excision with a bladder-cuff. Pathological study was consistent with metastatic renal cell carcinoma. The literature on ureteral metastasis from renal cell carcinoma is briefly reviewed and a mechanism for the metastasis is proposed.

[Changes in muscle activity of the lower extremities during forward-inclining-posture gait. Comparative study with free walking of healthy geriatric persons].

Using a force plate and electromyographic recordings, changes in the muscle activity of the lower extremities during forward-inclining-posture walking and the free walking of healthy young adults were studied and compared with the free gait of healthy geriatrics. The movement of the hamstring, and the tibialis anterior and calf muscles caused a negative quadric curve during the forward-inclining gait and a positive curve during the free walking. However, the movements of the rectus femoris muscle caused a positive curve during the forward-inclining gait and a negative curve during the free walking. It also was found that geriatrics are thrown off balance by changes in cadence while walking. Further, greater muscular activity of the lower extremities is needed by geriatrics than by young adults during free walking, and the muscular movements of geriatrics during free walking showed no relation to the forward-inclining muscular movements of the young adults.

Fate of circulating oxalate in rats.

The pharmacokinetics of oxalate were studied in normal and nephrectomized rats with the use of radioisotope-labelled oxalate. The disappearance of [14C]oxalate from the plasma was analyzed with a two-compartment open model. The pharmacokinetic parameters of oxalate were compared with those for inulin. In normal rats, the plasma half-life of the elimination of oxalate was 0.33 +/- 0.06 h and that for inulin was 0.26 +/- 0.05 h (n = 10, mean +/- SD). The volume of distribution for oxalate was 56.7 +/- 6.80 and that for inulin 34.0 +/- 4.79 ml/100 g body weight, indicating that oxalate has access to additional compartments besides the extracellular volume. The total clearance of oxalate was 1.2 times higher than that for inulin. In nephrectomized rats, however, the plasma half-life of the elimination of oxalate was 1.85 +/- 0.34 h (n = 7, mean +/- SD) and that for inulin was 4.26 +/- 0.78 h. The total clearance of oxalate was 177 +/- 29 and that for inulin was 30 +/- 5 microliters/min/100 g body weight. In order to identify the extrarenal elimination route of oxalate, the bile of nephrectomized rats was collected. The hepatic clearance of oxalate was 31.2 +/- 2.7 microliters/min/100 g body weight. The biliary excretion of oxalate accounts for 17.6% of the total clearance in nephrectomized rats. Thus, other elimination processes of oxalate besides renal and hepatic clearance take place.

Two cases of urothelial tumor with high serum level of carcinoembryonic antigen and TA-4.

Two rare cases of urothelial tumor with high serum carcinoembryonic antigen (CEA) and TA-4 levels are presented. One is a case of lymph node metastasis due to bladder tumor: pathological diagnosis revealed mucoepidermoid carcinoma. The other is a case of left renal pelvic tumor: pathological diagnosis revealed transitional cell carcinoma with glandular and squamous differentiation. The serum CEA and TA-4 levels, high before surgery, decreased after surgery.

[Combined effect of TNF and anticancer chemotherapeutic agents on murine bladder tumor (MBT-2)].

The antitumor activity of combination therapy of recombinant human tumor necrosis factor alpha (rHu-TNF alpha) and chemotherapeutic agents against murine bladder tumor (MBT-2) was studied. Tumors were intradermally transplanted into the hind leg of C3H-HeN mice and allowed to grow until they reached a diameter of 8 to 10 mm 10 days after transplantation. TNF (3,000 units) was given intraperitoneally from day 10 to day 19, and the chemotherapeutic agents, 5-FU (60 mg/kg), CPM (100 mg/kg), CDDP (10 mg/kg) and ADM (5 mg/kg), were applied once intraperitoneally on day 10. The antitumor effects were evaluated based on tumor volume on day 20. 5-FU, CPM and ADM enhanced the antitumor effect when combined with TNF, but CDDP did not. These findings suggest that combination therapy of TNF and certain antitumor chemotherapeutic agents is effective cancer treatment.

[Evaluation of the results of extracorporeal shock-wave lithotripsy (ESWL) for solitary upper urinary tract stone].

We performed extracorporeal shock-wave lithotripsy (ESWL) on 1,701 patients in a total of 2,438 sessions using the Dornier kidney lithotriptor Model HM III from July 1985 to the end of June 1990. Among the patients with a solitary stone, 1,200 cases were available for the follow-up study in which the results of ESWL were analyzed according to the location and size of the stone. ESWL performed against stones at pelvis and calyces gave the best results. The results obtained on stones less than 20 mm in diameter were especially favorable with a success rate of 84%. ESWL performed against ureter stones showed poor results with a success rate of 62% for the stones smaller than 20 mm in diameter. We further studied the results of ESWL performed against ureter stones by dividing the patients into three groups: the patients treated in situ, the patients with ureteral stents and the patients with D-J stents. The results for stones larger than 10 mm in diameter were significantly better in the patients with D-J stents than in the patients treated in situ or the patients with ureteral stents. Among the patients treated in situ, the results were significantly worse for impacted stones than for non-impacted stones when the stone size was 10-20 mm in diameter.

[Evaluation of the results of extracorporeal shock-wave lithotripsy (ESWL) for solitary upper urinary tract stone].

At Osaka City University Hospital, we performed extracorporeal shock-wave lithotripsy (ESWL) for 1277 patients in a total of 1788 sessions using Dornier kidney lithotripter Model HM III from July, 1985 to the end of December, 1988. Among the patients with a solitary stone, 911 cases were available for the follow-up study and we have compared the results among these cases in respect to the stone location and size. The results obtained were as follows: the ratio of kidney stone to ureter stone was found to be 2.2:1 in male, and 3.8:1 in female patients. This indicates that ureter stones are more frequently found in male than in female patients. In addition, we compared the size of kidney stones found in the patients including 415 male and 243 female patients. Stones larger than 20 mm were more frequently found in female than in male patients. Moreover, a stone composition study of these patients showed that the contents of both phosphate calcium and magnesium ammonium phosphate were higher in female than in male patients. ESWL performed against stones at pelvis and calyces exhibited the best results. The results obtained with the stones less than 20 mm in diameter were especially favorable with a success rate of 100% for the stones less than 10 mm and 83% for the stones 10-20 mm, in diameter, while the results with the stones larger than 20 mm in diameter were rather poor with a success rate of 31%. ESWL performed against ureter stones showed poor results with a success rate of 63% for the stones smaller than 20 mm in diameter.

[Experience with extracorporeal shock wave lithotripsy for urinary stone. Factors for requiring more than two ESWL treatments and its result].

Extracorporeal shook wave lithotripsy (ESWL) was performed for the treatment of 1277 urolithiasis patients at Osaka City University Hospital from July, 1985 to December, 1988. A total of 1788 ESWL treatments were carried out using Dornier HM3 kidney lithotripter. 964 patients (75.5%) underwent only one ESWL treatment, while 313 patients (24.5%) more than two ESWL treatments. We retrospectively examined the factors for requiring more than two ESWL treatments. Not only stone number, size and location, but fragility were considered to be the main causes for requiring more than two ESWL treatments. According to component analysis of ureteral stones, which were hard and resistant to shock wave, calcium apatite content of these stones turned out to be high (p less than 0.001). As for fragility, the residual stones created by ESWL were more difficult to be disintegrated that the nontreated stones of the same size (p less than 0.05). "Fragility" of the stones before shock wave and residual stones after ESWL are considered to be a major problem in ESWL treatment of urinary stones to be solved in the years to come.

[Side effects of extracorporeal shock-wave exposure on the kidney in the dogs].

The effects of extracorporeal shock-wave (SW) exposure on the kidney were investigated in dogs using a Dornier kidney lithotriptor HM3. The SW was generated by spark discharge at 20 KV and was focused on the lower part of either kidney. Before and after the exposure of 500 and 1000 shots of SW, the renal blood flow of the affected and contralateral kidney was measured by the microsphere method. The blood flow of the affected kidney decreased, but was comparable to that of the contralateral kidney immediately after the 1000 shots of SW. Renal scintigraphy using 99mTc-DTPA was performed before the exposure of SW, and 30 minutes, 1 week, 2 weeks and 4 weeks after the exposure. The renograms were evaluated by the following parameters: Tmax (time required to reach maximum radioactivity), RAmax ratio (maximum radioactivity of the affected kidney/that of the contralateral kidney) and T1/2 (the half-life of elimination). Tmax was significantly prolonged for the affected kidney 30 minutes after the exposure, while that for the contralateral kidney was shortened. The RAmax ratio was decreased 1 week after the exposure. T1/2 was significantly prolonged 30 minutes after the exposure, which was observed till 2 weeks later. The scintigraphy also showed a slight enlargement of affected site. The histological study showed a hemorrhage in the peritubular space, indicating rupture of the peritubular capillaries. In conclusion, the main effect of SW exposure on the kidney was the rupture of the peritubular capillaries, resulting in temporary and reversible deterioration of renal function.

[Clinical study on 32 patients who underwent parathyroidectomy at Osaka City University Hospital].

We retrospectively reviewed 32 patients who underwent parathyroidectomy at our hospital for the last fourteen years. 1) Clinical appearance of primary hyperparathyroidism was in younger age in women. 2) In previous history or at the time of PTX, 9 patients had malignant tumors including 6 thyroid cancers, 36% of the patients with out bone related symptoms had a remarkable decrease in bone mineral content. 3) After PTX, none of patients had recurrent urolithiasis and bone mineral content of all patients was significantly increased in a short time. In addition, upper GI complaints were improved, or hypertension was partially normalized. However, renal insufficiency remained unchanged. 4) In preoperative localization study, Ultrasound sonography (US) demonstrated the best accuracy rate of 88% when only one gland was involved. US was able to detect multiple gland involvement only in 20% of 5 cases. 5) Hypercalciuria was recognized as one of the risk factors of stone formation in patients with primary hyperparathyroidism.

Defective interleukin-1 production of monocytes in patients with bladder cancer.

Patients with advanced malignant neoplasms have a variety of abnormal lymphocyte and monocyte functions. We examined the PHA (phytohaemagglutinin) blastogenic response of lymphocytes and interleukin-1 (IL-1) production of monocytes in 40 bladder cancer patients and 16 control subjects. The correlation between the 2 parameters was also studied. The PHA blastogenic response was measured by the incorporation of 3H-thymidine into lymphocytes. IL-1 production was assayed by the murine thymocyte 3H-thymidine incorporation assay. As a result, the PHA blastogenic response and IL-1 production were significantly lower in the high stage bladder cancer patients compared to the control subjects and low stage patients. However, there was no significant correlation between the 2 parameters. Furthermore, with the addition of indomethacin, IL-1 production in the control subjects and low stage patients improved to the same degree, but it did not reach the control level in the high stage patients.

[Urolithiasis--a change in therapeutic methods extracorporeal shock wave lithotripsy using a Dornier kidney lithotripter HM3].

The kidney stone of less than 2 cm can be effectively treated by extracorporeal shock wave lithotripsy (ESWL) using a Dornier kidney lithotripter HM3 without any complication that might need other therapy. However, in the case of a large kidney stone and ureteral stone, there are some difficulties in the treatment with ESWL. To obtain better results for these stones with a Dornier kidney lithotripter HM3, in the patient having a large stone a double-J stent was placed and ureteral catheter was indwelling for the ureteral stone before ESWL. In some cases high frequency positive pressure ventilation (HFPPV) was applied to make respiratory movement of the stone minimum. An indwelling double-J stent can significantly decrease the necessity of auxiliary treatment and the incidence of high fever attack. Manipulation of a ureteral stone with a ureteral catheter did not facilitate stone disintegration, and also the success rate as compared with in situ ESWL. HFPPV can decrease the stone movement within 2 mm judged on the X-ray monitor and increase the effectiveness of the shock wave on the stone, leading to minimize not only shock wave dose but also side effects from shock wave exposure.

[A case of stone former with pacemaker treated by extracorporeal shock wave lithotripsy].

A stone former, a 60-year-old male with a pacemaker, was treated by extracorporeal shock wave lithotripsy (ESWL). He had been on a DVI pacemaker due to sick sinus syndrome since the age of 52. During treatment for left ureteral stone by ESWL, the pacemaker was stopped, since there was a possibility of extra systoles caused by coupled triggering of the shock wave with the pacemaker spike wave in ECG. Pulse and blood pressure were maintained by continuous drip infusion of phenylephrine chloride and isoproterenol. As a result, ESWL was accomplished and pacemaking was reestablished without any problem. KUB revealed that the patient became stone free on the postoperative 17th day.

[Experience with extracorporeal shock-wave lithotripsy of upper urinary tract stones].

The first 121 cases of upper urinary tract stone treated by extracorporeal shock wave lithotripsy (ESWL) at our clinic were analyzed. Three months after ESWL, 78% of the patients became stone free, and 17% of the patients had residual stone fragments which were less than 5 mm in diameter and considered passable. The success rate was therefore about 94.6%. No severe side effects were observed, although temporary elevations in serum creatinine phosphokinase, lactate dehydrogenase, glutamic-oxaloacetic transaminase, aldolase and total bilirubin occurred. These results indicated that ESWL was a safe and effective procedure for upper urinary tract stones.