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Biomedical subjects

M Murai

Publications and source records attributed to M Murai.

At least 145 records · Page 8Linked to original sources

High-intensity focused ultrasound energy for benign prostatic hyperplasia: clinical response at 6 months to treatment using Sonablate 200.

We evaluated the safety and efficacy of high-intensity focused ultrasound (HIFU) using a modified Sonablate 200 and compared the clinical response with that of the prototype Sonablate at 6 months after treatment. Since 1995, 35 patients ages 66 +/- 7 years underwent HIFU with the Sonablate 200 for symptomatic benign prostatic hyperplasia (BPH) under low spinal anesthesia. The estimated prostatic volume was 40.4 +/- 4.8 cc before treatment. A silicon-coated 16F latex catheter was indwelling during determination of the therapy zone and treatment so that critical tissue at the midline was thoroughly treated. Twenty-two patients were analyzed with complete 6-month follow-up data. Side effects were transient urinary retention in four of these patients, hematuria in five, and hematospermia in eight. Peak urinary flow rate increased from 7.4 +/- 4.0 mL/sec to 11.4 +/- 4.0 mL/sec (P < 0.001) (54% increase). During the same period, the mean International Prostatic Symptom Score decreased from 20.4 +/- 7.1 to 9.0 +/- 7.5 (P < 0.001) (56% decrease). Quality of Life score improved from 5.4 +/- 0.6 to 2.4 +/- 1.3 (P < 0.001). Magnetic resonance imaging by means of an endorectal surface coil revealed significant coagulative necrosis areas in the periurethral gland at 1 month on T2-weighted images. These data demonstrate that HIFU for BPH using the Sonablate 200 produced a better clinical response than the prototype Sonablate and is expected to provide long-term durability of the response.

Aged↗

Application of the interferon minipellet to human renal cell carcinoma in nude mice.

BACKGROUND: The interferon (IFN) minipellet is a sustained-release formulation of human lymphoblastoid IFN, with atelocollagen used as the carrier material. We evaluated the antitumor effect of the IFN minipellet on an established human renal cell carcinoma cell line (KU-2) transplanted in nude mice. METHODS: The treatment was started when tumor nodules had grown to 6 to 8 mm in diameter. The IFN minipellet, or an aqueous solution of IFN, was given by subcutaneous injection, or peritumor injection, on days 1 and 10. Antitumor effects were evaluated according to tumor weights calculated as (long diameter) x (short diameter)2/2 in 7 groups consisting of 6 mice each. RESULTS: IFN levels remained detectable in both tumor tissue and serum up to 10 days after peritumor injection of the IFN minipellet. Administered by the peritumor route, the IFN minipellet inhibited growth of the tumor significantly as compared with tumor growth in the untreated mice. The IFN minipellet showed greater inhibition of tumor growth by peritumor injection compared to subcutaneous injection. The aqueous solution of IFN was not effective either by subcutaneous or by peritumoral injection. CONCLUSION: Results indicate that the IFN minipellet is useful in the treatment of renal cell carcinoma.

Animals↗

Biochemical modulation of 5-fluorouracil with murine interferon-alpha/beta against murine renal cell carcinoma.

BACKGROUND: Conventional therapy for renal cell carcinoma using interferon (IFN) has shown limited antitumor action. The purpose of our study was to investigate synergistic antitumor effects of IFN and 5-fluorouracil (5-FU), and to elucidate the mechanisms of interaction between the 2 agents in mice. METHODS: Antitumor effects and biochemical modulation of murine IFN-alpha/beta and 5-FU were determined against the murine renal cell carcinoma cell line, Renca, in vivo. The activity of thymidylate synthetase and thymidine kinase was measured using cytosolic extracts of the tumors. RESULTS: Combination treatment with IFN-alpha/beta and 5-FU produced a significant enhancement of growth inhibition against Renca tumor. Treatment with 5-FU resulted in a 2.7-fold increase in the total amount of thymidylate synthetase and an 11.6-fold increase in the thymidylate synthetase inhibition rate, while the administration of IFN-alpha/beta did not significantly reduce the 5-FU-induced increase in thymidylate synthetase. The administration of IFN-alpha/beta decreased thymidine kinase activity to 65.5% maximally, compared with that in the control mice or the mice treated with 5-FU. CONCLUSIONS: The reduction of thymidine kinase caused by treating the mice with IFN-alpha/beta changes the utilization of exogenous thymidine for DNA synthesis, and may represent the mechanism of the additive antitumor effect of the 2 agents, through the suppression of the salvage pathway for deoxythymidine monophosphate induction.

Animals↗

Differential diagnosis of primary benign and malignant retroperitoneal tumors.

BACKGROUND: Clinical differential diagnosis between malignant and benign tumors is important in order to select a therapeutic strategy for a primary retroperitoneal tumor. METHODS: The clinical findings and radiological features of 25 patients with primary retroperitoneal tumors were retrospectively evaluated to find those signs that might contribute to the preoperative distinction between benign and malignant tumors. RESULTS: Of 25 primary retroperitoneal tumors, 15 were benign. This may reflect the increased number of incidentally found small benign tumors. There were significant associations between the presence of symptoms and malignancy (P < 0.05), between irregular margins on imaging and malignancy (P < 0.05) and between the absence of calcification and malignancy (P < 0.05). Malignant tumors were significantly larger than benign tumors (11.45 +/- 1.90 cm vs. 5.31 +/- 0.43 cm). A retroperitoneal tumor scoring system was developed to distinguish primary retroperitoneal benign tumors from their malignant counterparts based on the: 1) maximum diameter equal to or larger than 5.5 cm, 2) presence of symptoms, 3) absence of calcification, 4) presence of irregular margins, and 5) presence of cystic degeneration or necrosis. A significant correlation was found between the incidence of malignant tumors and the total retroperitoneal tumor score (P < 0.05). CONCLUSION: This study suggests that the size of tumor, the presence of symptoms, irregular margins, and the absence of calcification may be valuable predictors of primary retroperitoneal malignant tumor.

Adolescent↗

Angiomyolipoma: imaging findings in lesions with minimal fat.

PURPOSE: To investigate a method of diagnosing angiomyolipoma that contains minimal fat. MATERIALS AND METHODS: In six cases of angiomyolipoma with minimal fat, the attenuation on contrast material-enhanced and unenhanced computed tomographic (CT) images, the echogenicity on sonograms, the signal intensity on T2-weighted magnetic resonance (MR) images, and the gross configuration of the lesion were retrospectively analyzed. In 100 cases of renal cell carcinoma, the same parameters were analyzed, and results were compared with those of angiomyolipoma. RESULTS: When compared with the surrounding renal parenchyma, all six angiomyolipomas showed homogeneously high attenuation on unenhanced CT images, homogeneous enhancement on contrast-enhanced CT images, and homogeneous isoechogenicity on sonograms. Of the five angiomyolipomas examined with MR imaging, four were hypointense and one was isointense on T2-weighted images. All six angiomyolipomas protruded from the renal margin. None of the 100 renal cell carcinomas showed homogeneously high attenuation on unenhanced CT images, homogeneous enhancement on contrast-enhanced CT images, or homogeneous isoechogenicity on sonograms. CONCLUSION: In the kidney, homogeneously high attenuation on unenhanced CT images, homogeneous enhancement on contrast-enhanced CT images, and homogeneous isoechogenicity on sonograms are suggestive of angiomyolipoma that contains abundant muscle and minimal fat.

Adipose Tissue↗

A transient increase in serum procollagen 1 carboxyterminal peptide following effective treatment in prostate cancer patients with bone metastases.

Procollagen 1 carboxyterminal peptide (P1CP) is thought to be an indicator of new bone formation. The present report demonstrates that effective endocrine therapy induced an initial increase followed by a delayed decrease in serum levels of P1CP and alkaline phosphatase in spite of an immediate decrease in serum PSA and PAP and improvement of clinical symptoms in prostate cancer patients with bone metastases. The transient increase in P1CP and alkaline phosphatase is a healing reaction and is followed by apparent improvement. Short-term effects of endocrine therapy on prostate cancer patients with bone metastases should be comprehensively evaluated based upon the entire spectrum of clinical and laboratory findings including serial changes of serum prostate markers and bone markers as well.

Adenocarcinoma↗

ACTH-independent bilateral macronodular adrenocortical hyperplasia caused Cushing's syndrome.

A 53-year-old man who had been followed up for the treatment of hypertension presented with a bilateral adrenal mass during a screening CT scan. Other imaging studies and biochemical tests suggested Cushing's syndrome caused by a pituitary-independent and adrenal-dependent bilateral adrenal tumor. A total adrenalectomy was performed and the pathological appearance of the surgical specimen showed adrenal hyperplasia. Therefore, these findings were considered to be consistent with ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH). This tumor is quite rare and its etiology still remains controversial. We herein report this incidentally found AIMAH and also review the pertinent literature.

Adrenal Glands↗

Antitumor effects and pharmacological interaction of xiao-chai-hu-tang (sho-saiko-to) and interleukin 2 in murine renal cell carcinoma.

Conventional therapy for renal cell carcinoma using interleukin 2 (IL-2) has shown limited antitumor action. The purpose of our study was to investigate synergistic antitumor effects of IL-2 and Xiao-Chai-Hu-Tang (XCHT), and to elucidate the mechanisms of interaction between the two drugs against the murine renal cell carcinoma cell line, Renca, in vivo. The treatment was started 5 days after subcutaneous transplantation of Renca tumor. XCHT was given at a dose of 2.5 g/kg daily for 30 days orally. IL-2 was given at a dose of 10(4) U/mouse by subcutaneous injection every other day 8 times. Combination of XCHT and IL-2 inhibited growth of the tumor and prolonged survival significantly as compared with the untreated mice. Increased cellular infiltration was observed in tumor tissue and the lungs of mice treated with XCHT alone and by combination of XCHT and IL-2, but there were no histological changes in the liver and kidney. Elevation of serum IL-6 was observed in tumor-bearing mice, but IL-6 was significantly suppressed by administration of XCHT. The results obtained suggest that combination of XCHT and IL-2 induces enhanced immunological reaction in specific organs and tissues, and IL-6 may have a role in the synergistic effect of these two agents. It was concluded that combination of XCHT and IL-2 is useful in the treatment of patients with renal cell carcinoma.

Animals↗

[Spontaneous pyeloduodenal fistula: a case report].

A 71-year-old female presented with recurrent episodes of right flank pain and fever for the past several years. No pathogens were detected in the urine culture. Abdominal X-ray revealed staghorn calculi of the right kidney. Computerized tomography revealed pneumopelvis and staghorn stones of the right kidney. A nephrectomy was indicated based on the results of intravenous pyelography (IVP) and renogram which revealed a right non-functioning kidney. The adhesion of the right kidney with the duodenum and a transverse colon was so strong that a nephrectomy, a wedge resection of the duodenum and a transverse colectomy were performed. There was a fistula between the renal pelvis and the second portion of the duodenum. The fistula was speculated to have occurred by the spontaneous rupture of the renal pelvis to the duodenum. To the best of our knowledge, this is the 15th case of spontaneous nephroduodenal fistula in Japan.

Aged↗

Clinical experience with incidentally discovered pheochromocytoma.

PURPOSE: We reviewed 17 resected pheochromocytomas comprising 7 from symptomatic patients, and 10 unsuspected and incidentally discovered tumors. We compared various parameters concerning these 2 groups and investigated the features of the incidentally discovered pheochromocytoma. MATERIALS AND METHODS: Patient gender and age, clinical symptoms and signs, tumor localization, detection methods, findings on imaging studies, urinary catecholamine concentrations, results of metoclopramide stimulation tests, treatments at operation and tumor size were evaluated. Furthermore, we compared the clinically diverse aspects arising between the symptomatic and incidentally discovered pheochromocytomas. RESULTS: The 24-hour urinary noradrenaline and vanillylmandelic acid levels in the incidental cases tended to be lower than those in the symptomatic cases, while 24-hour urinary dopamine was significantly less (468 +/- 221 compared to 1,558 +/- 899 microg./day, respectively). Typical symptoms of pheochromocytoma were noted in 6 patients (60%) in the incidental tumor group. The incidental cases had a markedly high false-negative rate (71%) as noted by the metoclopramide stimulation test, although the symptomatic cases had a 100% positive rate. On the other hand, the average diameter of incidental tumors was significantly larger than that of the symptomatic lesions (55.5 +/- 19.1 versus 35.9 +/- 12.1 mm., respectively). CONCLUSIONS: Clinical signs and findings in patients with incidental tumors were weaker than those with symptomatic disease although most incidental tumors functioned. Lower urinary catecholamine values in the incidental tumors were consistent with these results. However, the surgical risk for incidental tumors was the same as that for symptomatic lesions. Therefore, patients with incidentally discovered pheochromocytomas scheduled to undergo surgery should be treated accordingly.

Adolescent↗

The value of serum carboxyterminal propeptide of type 1 procollagen in predicting bone metastases in prostate cancer.

PURPOSE: Carboxyterminal propeptide of type 1 procollagen (P1CP) is believed to be a marker of new bone formation. We investigated the possible application of serum P1CP as a biochemical marker for bone metastases in patients with prostate cancer. MATERIALS AND METHODS: Prostate specific antigen (PSA), prostatic acid phosphatase (PAP), P1CP and alkaline phosphatase were measured in 136 serum samples from 79 patients with untreated prostate cancer, 29 with stage D2 disease in remission and 28 with progressive stage D2 carcinoma. RESULTS: Serum P1CP and alkaline phosphatase were significantly elevated in untreated patients with a positive bone scan (278.9 +/- 61.9 ng./ml. and 826.5 +/- 176.3 international units per 1., respectively) compared to those with a negative bone scan (104.2 +/- 4.2 and 200.8 +/- 9.1, respectively, p <0.05). The areas under receiver operating characteristics curves were 0.86 for P1CP, 0.87 for alkaline phosphatase, 0.88 for PSA and 0.85 for PAP. The best accuracy rates for P1CP, alkaline phosphatase, PSA and PAP to predict bone lesions were 84, 87, 86 and 84%, respectively. P1CP provided a greater specificity and positive predictive value. These serum markers correlated significantly with the extent of disease on bone scan (p <0.05). The incidence of positive serum P1CP and alkaline phosphatase decreased significantly in response to endocrine therapy in patients with bone metastasis, and increased progressively in association with progression of the tumor (p <0.05) parallel to PSA and PAP. CONCLUSIONS: These findings suggest that serum P1CP is a useful indicator for predicting bone metastases.

Aged↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1995). III. Differences in susceptibilities from previous years].

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 11 hospitals during June, 1995 through May, 1996, and the results were compared with those obtained during the same period in earlier years. 1. Macrolide resistant E. faecalis isolated from uncomplicated UTIs during the latest study period appeared to have increased compared to those in previous study periods. More than 50% of the isolated E. faecalis during the latest study period were resistant to macrolide antibiotics, for the first time in our history. 2. No obvious changes were observed through the years for susceptibilities of S. aureus to various antimicrobial agents. Vancomycin (VCM) showed the highest activity against S. aureus, with MICs below 2 micrograms/ml or below. 3. Among E. coli strains, those with low susceptibilities to quinolones appeared to have increased over the years with MIC90 changed from between 0.125 microgram/ml or below and 0.5 microgram/ml in the 1989-1990 period to between 8 micrograms/ml and 128 micrograms/ml in the latest study period. 4. Klebsiella spp. showed higher resistance to most antimicrobial agents during periods of 1993-1994 and 1994-1995, but somewhat lower resistance during period of 1995-1996. No resistant Klebsiella spp. were detected from uncomplicated UTIs during the latest study period. 5. Among P. aeruginosa isolates from complicated UTIs, resistance isolates to gentamicin appeared to be increasing over the years. Resistant strains to quinolones were isolated at lower frequencies during periods of 1991-1994, but higher frequency was observed in the latest period, and MIC50s were between 0.5 and 4 micrograms/ml during 1991-1994, but were 16-32 micrograms/ml during 1995-1996. These susceptibility changes should be utilized in determining clinical treatments.

Anti-Bacterial Agents↗

[Embolization for massive retroperitoneal hemorrhage from adrenal pheochromocytoma: a case report].

A 68-year-old woman was found crouching in the kitchen with severe upper abdominal pain. She entered a state of shock at our emergency clinic. Abdominal computed tomography (CT) scan demonstrated a 3 cm cystic mass dorsal to the pancreas tail accompanied with a hematoma. On angiography, a bleeding from the left middle adrenal artery was identified and embolized for hemostasis. An operation was performed 3.5 months after embolization. Preoperative evaluation showed the tumor to be endocrinologically inactive. Metoclopramide stimulation test was negative, too. Left adrenalectomy was performed uneventfully without intraoperative increase in blood pressure. However, histopathological diagnosis was pheochromocytoma. Transarterial embolization is an effective treatment for adrenal bleeding. In our case, however, embolization might have caused the tumor to be falsely "endocrinologically inactive".

Adrenal Gland Neoplasms↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1995). I. Susceptibility distribution].

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 704 bacterial strains isolated from patients with urinary tract infections (UTIs) in 11 hospitals during the period of June 1995 to May 1996. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.8% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.2% and most of them were Escherichia coli. Susceptibilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) and imipenem (IPM) showed the highest activities against E. faecalis isolated from patients with UTIs. The MIC90S of them were 1 microgram/ml. Vancomycin (VCM) and piperacillin (PIPC) were also active with the MIC90S of 2 micrograms/ml and 4 micrograms/ml, respectively. The others had low activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM showed the highest activities against S. aureus isolated from patients with UTIs. Its MIC90 was 1 microgram/ml against both S. aureus and MRSA. Arbekacin (ABK) was also active with the MIC90 of 2 micrograms/ml. The other except minocycline (MINO) had very low activities with the MIC90S of 64 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and MINO showed the strongest activities against S. epidermidis isolated from patients with UTIs. The MIC90S of them were 0.25 microgram/ml. VCM was also active with the MIC90 of 1 microgram/ml. The MIC90S of cephems ranged from 2 micrograms/ml to 16 micrograms/ml in 1994, but they ranged from 8 micrograms/ml to 128 micrograms/ml in 1995. These results indicated that some resistances existed among S. epidermidis to cephems. 4. Streptococcus agalactiae All drugs except gentamicin (GM) were active against S. agalactiae. ABPC, cefmenoxime (CMX), IPM, erythromycin (EM), clindamycin (CLDM) and clarithromycin (CAM) showed the highest activities. The MICs for all strains were lower than 0.125 microgram/ml. The MIC90S of the others were 2 micrograms/ml or below. 5. Citrobacter freundii IPM showed the highest activity against C. freundii isolated from patients UTIs. Its MIC90 was 1 microgram/ml. GM was also active with the MIC90 of 2 micrograms/ml. Cefpirome (CPR), cefozopran (CZOP) and amikacin (AMK) were also active with the MIC90S of 4 micrograms/ml. Penicillins and cephems except CMX, CPR and CZOP showed low activities with MIC90S of 256 micrograms/ml or above. 6. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. MINO and tosufloxacin (TFLX) were also active with the MIC90S of 8 micrograms/ml. Penicillins and cephems except CPR and CZOP showed lower activities with the MIC90S of 256 micrograms/ml or above. 7. Escherichia coli. Most of the antimicrobial agents were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MICs for all strains were equal to or lower than 0.5 microgram/ml. CMX and TFLX were also active with the MIC90S of 0.125 microgram/ml or below. Penicillins were slightly active with MIC90S of 128 micrograms/ml or above. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with MIC90S of 2 micrograms/ml or below. Carumonam (CRMN) had the strongest activity against K. pneumoniae, the MICs for all strains were equal to or lower than 0.125 microgram/ml. Comparing with the result of 1994, the sensitivities of K. pneumoniae against all drugs had obviously changed into a better state. For example, the MIC90S of cephems ranged from 0.25 microgram/ml to 16 micrograms/ml in 1994, but they were all lower than 2 micrograms/ml in 1995. 9. Proteus mirabilis P. mirabilis was susceptible to a majority of drugs. CMX, ceftazidime (CAZ), cefixime (CFIX), and CRMN showed the highest activities against P. mirabilis isolated from patients with UTIs. MICs of CRMN for all

Anti-Bacterial Agents↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1995). II. Background of patients].

Clinical background was investigated on patients with urinary tract infections (UTIs) from whom 785 bacterial strains were isolated in 11 hospitals during the period from June, 1995 through May, 1996. 1. Distributions of age and sex of patients and type of infections. Among the patients examined, those with ages 50 years or older were the most frequent (males: 80.5%, females: 69.7%), and, among females, those with ages in the 20's were 12.6%. With regard to types of infections, more than a half of infections among males were of complicated types, but most of infections among females were of uncomplicated types, especially among females of ages less than 60 years. 2. Ages of patients and types of pathogens. The higher the ages of patients, the lesser became the isolation frequencies of Proteus spp. and Serratia spp., but the higher were those of Klebsiella spp. and Pseudomonas spp. 3. Effect of antibiotic use on isolation frequencies of pathogens. Use of antibiotics decreased pathogens isolated from patients with uncomplicated UTIs drastically (237 isolates before antibiotics compared to 33 after). Even isolated pathogens from patients with complicated UTIs decreased drastically with the use of antibiotics when indwelling catheters were not in use (200 isolates before antibiotics compared to 83 after), but when indwelling catheters were in use, antibiotics apparently failed to decrease the isolation frequency. 4. Surgical procedures and types of causative organisms for UTIs. Escherichia coli was the most frequently isolated organism from uncomplicated cases of UTIs. From cases of complicated UTIs without indwelling catheters, Enterococcus faecalis was the most frequently isolated, followed by E. coli, P. aeruginosa and Klebsiella spp. When a surgical procedures were not done, E. coli was isolated most frequently. From cases of complicated UTIs with indwelling catheters, P. aeruginosa, E. faecalis and S. aureus were the organisms that were mainly isolated, with isolation frequencies of 23.9%, 17.3% and 12.7%, respectively. When no surgical procedures were used, isolation frequencies of P. aeruginosa, Klebsiella spp. and E. faecalis were 25.7%, 14.3% and 14.3%, respectively.

Adolescent↗

Yearly variation of spontaneous somatic mutation frequency in the stamen hairs of Tradescantia clone KU 9 grown outdoors, which showed a significant increase after the Chernobyl accident.

Scoring of spontaneous somatic pink mutation frequency in the stamen hairs of Tradescantia clone KU 9, a heterozygote for flower color (blue/pink; the blue color being dominant), was carried out for 11 years on plants grown outdoors, during the period of May 11-31 (for 3 weeks) in every year from 1982 to 1992. Weekly and yearly variations of the spontaneous mutation frequency were observed, and such variations could mostly be correlated to the difference in temperature. That is, the mutation frequency was generally higher in the weeks and years when the temperature was relatively low, showing the strongest negative correlation with the average minimum temperature. The variations were also correlated to the diurnal temperature difference, the mutation frequency being higher with larger diurnal temperature difference in general. However, the mutation frequency observed in 1986 was exceptionally higher than that expected from the temperature for this year, and was very significantly higher than for other years. The scoring of mutation frequency was thus continued in 1986 for an additional 4 weeks (June 1-28), and it was confirmed that such higher mutation frequencies lasted for 6 weeks in total. The exceptionally high mutation frequency seemed to be related to the radioactive fallout which occurred in early to mid May of 1986, even in Japan, after the serious nuclear reactor accident at Chernobyl, and also to the biological concentrations of radioactive nuclides which subsequently occurred, although it was difficult to conclude this definitely. The mutation frequency in 1987 was second highest, and was also significantly higher than the lowest mutation frequency observed in 1990.

Climate↗