In the present study, testis tissues were obtained from patients (in 23 cases) of idiopathic male infertility whose semen specimens were diagnosed to be either oligozoospermia or azoospermia. Testis tissues were furthermore obtained from patients (in 4 cases) of cryptorchism, eunuchoidism, bilateral congenital absence of the vas deferens and postvascectomized azoospermia. At the time of each surgical procedure, control specimens were dissected out from 6 individuals who were not clinically suffering from idiopathic male infertility. In all cases, Charny's accepted biopsy technique was employed. The tissue specimens were subjected to the following three types of fixation, 1) Carnoy's fluid (for 2 hours at room temperature), 2) 1% cetylpyridinium chloride (cpc) in Carnoy's fluid (for 2 hours at room temperature) and 3) 1% cpc in Carnoy's fluid (for 2 hours at room temperature) following treatment with cpc-urea for 2 hours at 53°C. After fixation, all the tissue specimens were embedded in paraffin and then stained with hematoxylin-eosin for general observation as well as the following histochemical methods for the demonstration of complex carbohydrates: 1) alcian blue (AB) (pH 1.0), 2) AB (pH 2.5), 3) dialyzed iron ferrocyanide (DI-FCY), 4) periodic acid-Schiff (PAS). For identifying individual acidic and neutral carbohydrates, the following procedures of enzyme digestion were performed upon some tissue sections prior to histochemical staining, a) sialidase [prior to staining with AB (pH 2.5)], b) streptomyces hyaluronidase [prior to staining with AB (pH 2.5)], c) testicular hyaluronidase [prior to staining with AB (pH 1.0) or (pH 2.5)], d) chondroitinase ABC [prior to staining with AB (pH 1.0) or pH 2.5)], e) chondroitinase AC [prior to staining with AB (pH 1.0) or (pH 2.5)], f) α-amylase [prior to staining with PAS].
The results are summarized as follows:
1) The seminiferous tubular walls and interstitial connective tissue in the testis tissues from both the normal and infertile individuals were believed to contain acidic complex carbohydrates with sulfate esters and carboxyl groups.
2) The present effects of digestion with chondroitinase ABC and AC upon AB (pH 1.0 and 2.5) reactions of the seminiferous tubular walls in the testis tissues from normal individuals and patients of male infertility were taken to indicate the presence of isomeric chondroitin sulfates (A and/or C) in these structure.
3) The interstitium of the testis tissues from normal individuals and patients of male infertility contained chondroitin sulfate B.
4) According to the present results obtained by the PAS staining procedure employed in combination with digestion with α-amylase, the germinal and supporting cells in the infertile testis tissues were thought to contain a large amount of glycogen than those in the cells in normal testis tissues.

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In the testis tissues from patients of idiopathic male infertility, complex carbohydrates have been histochemically studied by the light microscopic method, in comparison with the substances in tissues from normal individuals. In the present work, Peroxidase labeled-Ricinus communis agglutinin-diaminobezidine (PO-RCA-DAB), Concanavalin A-peroxidase-diaminobenzidine (Con A-PO-DAB), Con A-PO-DAB-periodic acid-m-aminophenol Fast black salt K (PA-AP-FBK) reactions and protein reactions are employed histochemically. In the infertile testis tissues and normal tesis tissues, the seminiferous tubules and interstitium contain an appreciable amount of α-D-glucose and α-D-mannose. In the seminiferous tubulus and interstitium of the idiopathic male infertile testis tissues, another histochemical property of primary importance was the galactose deficiency in complex carbohydrates involved, which are in nature a glycoprotein containing only small amounts of sulhydryl and disulphide groups. The results of the present study indicate that the PO-RCA-DAB procedure is useful in diagnosing the idiopathic male infertility.

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For the purpose of investigating urination ability, uroflowmetry and UPP measurement under fluoroscopic visualization by means of X-ray television, was done on 40 patients suffering from dysuria, but having no clear adenoma of prostate, mainly before and after transurethral resection of the small resistant part against urination in the posterior urethra.
Their age distribution was from 50 to 84 years old, on average 69 years old.
In the patients having indication for TUR, because of the organic changes in their posterior urethra, (small adenoma of prostate or bladder neck contracture), their urination ability was much improved after TUR, but no correlation was found between the weight of the removed tissue and the degree of restoration for their urination ability.
Moreover, in 10 cases showing slight depression of voiding ability measured by uroflowmetry, but without any organic causes in their cervical portion of the bladder, the causes of their dysuria and the therapies were described.
The reasons why the area under the UPP curve was not always proportional to the volume of prostatic benign adenoma and elevation of its curve at the cervical portion of the bladder was not specific to the patients with bladder neck contracture were investigated and partly clarified by this urethral pressure profilmetry under fluoroscopic visualization.
In conclusion, for the patients of old age suffering from dysuria, even if the organic changes in their posterior urethra were small, the transurethral resection of such obstacles, if possible, is thought to be a better remedy for them than other conservative therapies.

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Congenitally dilated ureters (32 cases) were urodynamically and histopathologically investigated. In the majority of instances the pathogenetic significance of the distal narrowed segment was reconfirmed. Difference in the development of the ureteral sheaths was also incriminated as a contributing factor in the genesis of these ureteral dilation—the more than well developed deep sheath by inherently constricting the terminal ureteral end in the non-refluxing (primary) megaloureter, and their poor development by allowing free reflux in the refluxing megaloureter. 5 cases (4 infants, 1 adult) of non-refluxing megaloureter and 1 infantile case of refluxing megaloureter were also described as unusual ones by demonstrating functional and morphological evidence of severe dysplasia of the dilated ureteral wall.
Clinical materials in the last 14 years and their data are illustrated in Table 1. At the time of surgery prospective study was started from 1974 to elucidate functional features of the obstruction by pressure flow study (PFS) with empty and full bladder, respectively. The ureteral end was then freed from the bladder wall by meticulously dissecting along the plane of Waldeyer's space. Operative specimen from the distal ureteral end inclusive of the ureteral orifice and dilated portion were submitted to detailed histological study by both light and electron microscopic methods. The followings are the results of this prospective study of 34 ureters in 32 cases.
Undisputed obstruction, namely progressive elevation of pressure in PFS with or without bladder distension, was documented only in 3 infantile cases of non-refluxing megaloureter. All the remainder, regardless of arbitary classification of refluxing versus non-refluxing megaloureter, failed to show obstructive effect when the bladder was continuously drained. When the bladder was not drained, however, they proved to be truly obstructed ureters as demonstrated by cinefluoroscopy and PFS. After the ureter was disconnected from the bladder, its ureteral end was no longer obstructive even when the bladder was filled to its capacity. Reuxing megaloureter in association with paraureteral diverticulum appeared to belong to reflux with obstruction as seen in delayed emptying of the refluxed urine.
Histologically condition of extrinsic ureteral muscle, namely the ureteral sheaths, differs in the refluxing and non-refluxing mugaloureter. Its development was inconspicuous in the former, while it was more than well developed in the majority of the latter, this being more aptly so in their deep sheath. Regarding the intrinsic ureteral muscle, however, they generally shared common microscopic feature by demonstrating either total disarrangement, predominantly circular orientation, normal or hypoplastic development of the narrowed segment with or without increase in the interstitial connective tissues. Meanwhile in the dilated portion muscular integrity and interstitial feature were relatively normal except for some evidence of hypertrophy and hyperplasia and/or fibrosis. Ultrastructural apparatuses such as thick and thin filaments in the individual muscle cell, nerve fibers and nexuses were uniformly observed to be normal throughout the whole length of the ureter. An exception to these general feature of ureteral musculature was noted exclusively in the 5 infantile and 1 adult cases including 3 cases discussed previously as cases of undisputed obstruction. The dilated portion was characterized by sparse distribution of muscle cells with an increase in the interstitial connective tissue. Individual muscles, scattered among large amount of collagenous fibers, were much smaller than those of the narrowed segment and lacked nearly all thick myofilaments. Nerves were seen as well as nexuses, the latter being attenuated however. These contrasted well to the histopathology of the narrowed segment which was characterized by relative normalcy in regard to musculointerstitial arra

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During 18 months from April 1977 to September 1978, 222 clinical isolates of Serratia marcescens obtained from Niigata University Hospital were microbiologically examined and the results were summarized as follows:
1) One-hundred and twenty-two strains were isolated from urine, 44 strains from sputum and 56 strains from the other specimens. The number of isolates increased in 1978 as compared with those of the preceding year.
2) One-hundred and ninety-five strains (87.8%) were typable serologically. The serotype O-2 and O-3 were frequent in urine, O-8 in sputum, and O-2 and O-8 in the other specimens.
3) In 20 strains which produced prodigiosin and in 13 strains which were resistant to penicillin, bacteriophages were isolated and the phagetyping was performed. However, there was no significant finding between the origin, serotype and phagetype of the strains.
4) All strains were examined for sensitivity to 26 drugs. “Urinary” strains were found to be higher in prevalence rate of resistant strains. In general, Serratia strains tested were resistant to PCG, MCIPC, CET and CEZ, and sensitive to aminoglycosides, including AMK and GM. However, some isolates in 1978 became resistant to the latter.
5) Cephalosporinase was produced by almost all strains tested. However, penicillinase was produced by 90% of “urinary” strains, respiratory strains and 25% of the other strains. Chloramphenicol acetyltransferase was demonstrated in one strain which was highly resistant to CP.
6) The drug resistance of Serratia to PC, SM, TC and CP was transferable to Escherichia coli at a frequency of 1×10^-5. And the resistance of the transconjugant was eliminated by ethidium bromide in 80%.
Besides, the transmission of resistance between strains of S. marcescens was also demonstrated.

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Although TUR-Bn has been accepted as a useful method for various bladder neck obstruction, the cutting position to improve urinary flow seems to be still disputable. To clarify the influence of cutting on the urinary flow, the present work was undertaken using adult female dogs, and the following results were obtained.
1) The urine flow resistance was decreased by the resection at 6 and/or 12 o'clock position of the bladder neck.
2) The urine flow resistance was increased by the resection at 3 and/or 9 o'clock position of the bladder neck.
These results suggested that the resection site of 3 and 9 o'clock position in TUR-Bn interferes the bladder neck opening mechanism.

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The calcium metabolism was investigated from electrolyte and endocrinological point of view in 109 male subjects with calcium urolithiasis and 37 normal male subjects without such a history.
1) The urine calcium excretion was higher in stone formers than in control subjects. [173±89mg/day (mean±SD) vs. 134±77mg/day, P<0.01]. Stone formers were classified into two large groups with 288mg/day [mean±2SD of control urinary calcium excretion] as the border line between groups.
2) Urinary cyclic AMP excretion, plasma parathyroid hormone (PTH), and renal tubular reabsorption of phosphate (%TRP) were lower in hypercalciuric stone group than in normocalciuric stone group. These phenomena suggest that the parathyroidal function of the hypercalciuric stone group is suppressed.
3) There was a significant negative correlation of urinary cyclic AMP excretion with urinary calcium excretion in the control group (P<0.01), but not in the normocalciuric stone group. Therefore, we classify normocalciuric stone formers into three groups according to urinary cyclic AMP and urinary calcium excretion for three days. Type I; Increased urinary cyclic AMP is accompanied by decreased urinary calcium. Type II; Increased urinary cyclic AMP is accompanied by increased urinary calcium. Type III; The other patterns between both urinary excretions.. In only Type I of normocalciuric stone group (81 cases), negative correlation could be demonstrated between both urinary excretions (P<0.05). However, in Type II (7 cases), the urinary excretion of cyclic AMP was correlated positively with urinary calcium excretion as hyperparathyroidism (P<0.01).
These reports suggest that there is a clear difference in the mechanism of stone formation between Type I and Type II. In Type I, the change of calcium values may follow one of parathyroidal function, while in Type II, parathyroids may have an initiative in calcium and parathyroidal metabolism, and have a major effect of some sort on urolithiasis and factors such as matrix, which appear to play a major role.
4) There was a strong negative correlation between %TRCa⁺⁺ and urinary calcium excretion in Type I (P<0.001), but some cases of Type II were plotted far from the regression line, and no correlation could be obtained in Type II.
5) Positive correlation could be demonstrated between cyclic AMP content of renal cortex and urinary cyclic AMP excretion, and negative correlation between cyclic AMP content of renal cortex and urinary calcium excretion. Cyclic AMP content was larger in renal cortex than in renal medulla. These results suggest that parathyroid hormone may act on the renal cortex and, therefore, urinary cyclic AMP is supposed to be the second messenger of PTH.
6) Urinary magnesium excretion was significantly higher in hypercalciuria than in normocalciuria (P<0.05). There was a strong positive correlation between the urinary excretion of magnesium and calcium in the stone former group (P<0.01).
Significant correlation could not be found between the urinary cyclic AMP excretion and the electrolytes except for urinary calcium.
7) There was no significant difference between the urinary cyclic AMP of single stone formers and recurrent (and/or multiple) ones. The urinary excretion of calcium was slightly higher in recurrent stone formers than single ones, but this difference was not significant.

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Fifty-eight male patients with calcium urolithiasis (nine hypercalciuric stone formers and fortynine normocalciuric stone formers) and seventeen normal male subjects were studied with a calcium restricted test and an oral calcium tolerance test.
1) Calcium restricted test; Each subject underwent calcium restricted test after four days of adherence to instricted diet, resticted in calcium to about 200mg/day, sodium to about 3500mg/day and phosphate to about 1000mg/day. The excretion of urinary calcium was remarkably decreased, and that of urinary cyclic AMP was increased in the hypercalciuric stone group. However the same result could not be obtained in the control group and normocalciuric stone group. In hypercalciuria, %TRCa⁺⁺ was increased, but filtered calcium was unchanged by calcium restricted test. In control and normocalciuria, %TRCa⁺⁺ nor filtered calcium were not found to be unchanged.
These results suggest that it may be useless to treat normocalciuric stone formers with calcium restricted diet and cellulose phosphate, and the parathyroid function of hypercalciura is suppressed.
Urinary magnesium excretion was decreased by calcium restricted diet in only hypercalciuric stone formers. Serum phosphate was extremely increased in all three groups.
2) Calcium tolerance test; This test was performed on the next day of calcium restricted test.
Fifty-eight male patients with calcium urolithiasis (nine hypercalciuric stone formers and forty-nine normocalciuric stone formers) and seventeen normal male subjects were studied with a calcium restricted test and an oral calcium tolerance test.
After an overnight fast from 9PM, a two hour fasting urine sample was collected from 7AM to 9AM. At 9AM 1gm calcium was given orally with 300ml of distilled water. Urine was collected in four hour pools from 9AM to 1PM. Venous blood was obtained without stasis at 8AM and 11AM.
The urine calcium excretion and serum calcium were remarkably increased in all three groups. Especially after the calcium load these value of hypercalciuria was significantly different from that of control and normocalciuria, although there was a significant difference among the three groups in urine and serum calcium of the fast. From this result, it is assumed that hypercalciuric stone formers not only take calcium more than normocalciuria, but also have the mechanism of more calcium absorption in the intestine.
The urinary cyclic AMP and plasma PTH was significantly decreased in the control and normocalciuric group, but these phenomena could not be found in hypercalciuria. It is supposed that this result causes a suppression of parathyroid function of hypercalciuria as described formerly. The nonsignificant decrease of parathyroid function may cause a significant increase of serum calcitonin in hypercalciuria.
3) I found the hypercalciuric patient metabolism from the other hypercalciuric patients. His fasting urinary calcium was not decreased. The values of his urinary cyclic AMP and serum PTH were the highest among hypercalciuric patients, and the serum calcium was slightly low.
Calcium restricted diet did not cause a decrease of the urinary cyclic AMP, but it was extremely decreased by oral calcium torelance test.
These results suggest that in this case calcium reabsorption disturbances may arise because of abnormalities in the renal tubulus, namely renal leak hypercalciuria.
The endocrinological state of this case may be a secondary hyperparathyroidism. However, hypercalciuric patients were mostly caused by an increase in calcium absorption in intestine, i. e, absorptive hypercalciuria.

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The comparison between the measured value of ionized calcium (Ca⁺⁺) by means of the selective ion sensitive electrode and the calculated value by the computor was performed with particular interest in the effect of citrate on the precipitation of calcium phosphate.
The mean value of measured %Ca⁺⁺/total calcium was 42% in the artificial urine at pH 5.7 and 39% in the urine of five normal subjects at pH 6.0. The calculated value in artificial urine was 53% at pH 6.0. Among the components of artificial urine, citrate was the most effective to decrease Ca⁺⁺, which was followed by sulphate and phosphate. As an exception magnesium increased Ca⁺⁺. The precipitation in the calcium and phosphate containing solution could be detected by the sudden decrease of Ca⁺⁺, which could be observed by only the measured value. The calculated value showed no information concerning the precipitation. The Ca⁺⁺ decreasing effect of citrate became predominant according to the increasse of pH and reached almost the maximum at pH 8. The precipitation point, pH at which the precipitation occurred, moved apparently to a more alkali side by the application of citrate.
The possible application of citrate to urolithiasis was discussed on the basis of the present findings.

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The light and electron microscopic changes were studied in ten cases of bladder tumor before and after hyperthermic vesical irrigation of bleomycin. Three of the 10 cases were previously treated by intravesical instillation of bleomycin. These specimens were also studied. Clinically hyperthermic vesical irrigation of bleomycin caused tumor disappearance in 4 cases, tumor decrease in 4 and no change in 2. The tumors recurred in 2 of 4 cases with complete disappearance.
Ultrastructural changes of the tumor cells in intravesical instillation and hyperthermic irrigation of bleomycin were essentially similar. The changes, however, were more striking in the latter therapy. Ultrastructural changes of the well differentiated tumors after treatment were as follows: The cell appeared swollen and cytoplasmic matrix became electron lucent with a decrease of cytoplasmic organelles especially of rough endoplasmic reticulum and of Golgi apparatuses. The swollen mitochondria and vesicles of various sizes were scattered. Nuclear matrix became electron lucent and a decrease of chromatin granules was apparent. The nucleolus either disappeared or enlarged with prominent reticular nucleolonema. Enlarged nuclear bodies were also observed. There were cells with an increased number of lysosomes and bundles of microfibrils. The cells with very dense cytoplasm and nucleus were often encountered and considered as degenerating cells. Intercellular spaces appeared to be dilated and the separation of tumor cells became evident. Bleb formations were observed at the free cell surfaces. When a tumor grossly disappeared after treatment, TUR of bladder mucosa was performed in the area of the original tumor site. The luminal cell surfaces in these regions failed to show the scaphoid plaques of asymmetric unit membranes, which featured the normal vesical superficial cells. One poorly differentiated tumor did not respond to the treatment, although similar ultrastructural changes were observed.
The results indicated that hyperthermic vesical irrigation of bleomycin induced a condensation and degeneration of the tumor cells. The suggested mechanism of tumor reduction was clinically supported by the fact that the treatment was effective in small papillary tumors less than 10mm in diameter.

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Although erectile impotence has been clinically classified into the one with functional cause and the organic one, the precise and objective method for the diagnostic evaluation of impotent patients has not yet been established. Therefore, the development of diagnostic methods of impotence is vitally expected. Since the penile erection is known to be one of the concomitants of REM sleep, the authors monitored this phenomenon during sleep (REM-Penogram: REM-P in abbreviation) in impotent patients and examined the possibility of its application to the clinical diagnosis of impotence.
All-night polygraphic recordings were carried-out on 3 male healthy subjects, 5 male impotent patients with functional cause and 5 with organic one. The REM-P was recorded using a strain-gauge filled with active charcoal in elastic tubing devised by Matsumoto et al, and the authors equipped the penis-root of the subjects with the strain-gauge. In order to determine wakefullness, Non-REM sleep and REM sleep, EEG, eye movements, chin muscle activity, respiration and heart rates were simultaneously recorded together with penile erection.
The following results were obtained:
1) In both the normal subjects and the functional impotent group, REM sleep was observed 3-5 times per night in all the cases except one, and the rate of the occurrence of the complete erection was in about 85% of episodes of REM sleep.
2) In the impotent group due to organic cause, no complete erection except one (case 9) was observed. The case 9 was the only example which recovered from impotence gradually during observation process by the follow-up of the recordings of REM-P.
The authors, like the Karacan's group, suggest from these results that REM-P is applicable to make a differential diagnosis of impotence, that is, to determine whether erectile dysfunction is due to organic cause or not.

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The neurological approach of physiologic erectile mechanism has not been made enough. However, if the erection is observed in the records of REM-P (see Report 1.) in impotent patients, the authors consider that at least no disorder is found in the nervous and circulatory systems concerning the erection at the level below the brainstem. Up to now, there have been many reports that the trouble of the brainstem has something to do with the sequelae after cranial trauma. Moreover, considering the fact that most of the sexual behavior accompanied with erection are controlled at the limbic system and the hypothalamus, there may exist patients with erectile dysfunction caused by disorders of the hypothalamusbrainstem system.
Under these considerations, the recordings of REM-P and the tests of Brainstem-Function (BSF in abbreviation) were made on 36 impotent patients, and the relationship between the hypothalamusbrainstem system and erectile dysfunction was investigated. BSF was examined with special reference to Optokinetic nystagmus test, Eye tracking test and Adrenalin loading test.
The following results were obtained:
1) The abnormal BSF was noticed in 24 cases out of 36 (66.7%).
2) In the organic impotent group, the abnormal BSF was noticed in 11 cases out of 13 (84%), this percentage was significantly higher as compared with that of the abnormal BSF in the functional impotent group, namely, 13 cases out of 23 (57%).
3) In the functional impotent group with incomplete erection during REM sleep, the abnormal BSF was found in 5 cases out of 13 (38%), while, in the case with complete erection during REM sleep, the abnormal BSF was noticed in only one case out of 10.
From the results summarized above, it is suggested that the existence of abnormal state in the hypothalamus-brainstem system may be one of the factors preparatory for inducing impotence. Attempts to elucidate factors responsible for erectile dysfunctions should be directed toward determining whether the disorder in the hypothalamus-brainstem system causes impotence or it occurs simultaneously at the onset of impotence.

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Hypertrophy and hyperplasia of the remaining kidney in response to unilateral nephrectomy were studied, analyzing patterns of changes in DNA, RNA and protein contents. Sixty rats were subjected to surgical excision of right kidney, and 20 rats were subjected to detachment of right kidney from its surrounding tissue as sham-operated controls. On the 1st, 3rd, 5th and 7th day after the nephrectomy, 15 each of the rats were sacrificed. Removed kidneys were weighed, seperated into cortex and medulla, and minced. Parts of minced cortex and medulla were used for estimation of DNA, RNA and protein. From the remnants of minced cortex, tubules were isolated by collagenase treatment and sucrose density centrifugation. The minced cortex was incubated in Hanks' solution containing 0.1% collagenase (Type I, Sigma Co.) at 37°C for 25min, and filtered through two layers of nylon gauze. Large aggregates were further incubated with collagenase and filtered. The filtrates were combined, and centrifuged for 1min at 50g. The pellet was washed three times with Hanks' solution by suspension and centrifugation. The final pellet was suspended in Hanks' solution, and layered on a discontinuous sucrose gradient (75%, 57% and 8.6%w/v). After centrifugation for 60min at 1, 000g, the fragments concentrated at the interface between 57% and 8.6% layers were collected as a tubular fraction.
DNA, RNA and protein were measured by Burton's method, orcinol method and Lowry's method, respectively. In order to compensate for individual differences, the values were usually expressed as the ratio of the values of the left kidney to those of the right.
Nephrectomy induced a compensatory enlargement of the remaining kidney. An increase by 20% in weight of the remaining kidney was observed within 7 days after nephrectomy, and the extent of the increase was similar in cortex and medulla. In cortex, total RNA and protein contents increased on the 1st day after nephrectomy, and the increase continued almost linearly up to the 7th day, while total DNA content increased on the 3rd day, but slightly thereafter. Thus, a decrease in DNA concentration (mg/g wet tissue) and increase in RNA/DNA and protein/DNA ratios, except on the 3rd day, were noticed. These results suggest that hypertrophic response began on the 1st day and continued at least up to the 7th day, in addition to hyperplastic response, provoked on the 3rd day. On the other hand, behaviors of macromolecular contents in the medulla after nephrectomy were characterized by almost linear increments in total RNA and protein contents, and a decrease in DNA concentration throughout the experimental period. The increase in total DNA content was very slight. Therefore, the enlargement of the medulla induced by nephrectomy appeared to be attributed mainly to hypertrophy, and slightly to hyperplasia.
Since recovery of tubules in the isolation method was not quantitative, behaviors in total DNA, RNA and protein contents were not measurable. However, an increase in RNA/DNA ratio in tubules after nephrectomy was remarkable, while an increase in protein/DNA ratio was obscure. These results suggest that nephrectomy induces hyperplastic, more than hypertrophic response in tubules of the remaining kidney, because hypertrophy is expected to be accompanied with remarkable increment in protein/DNA ratio.
Clinical significance of this compensatory response was discussed.

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