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Biomedical subjects

A Bergqvist

Publications and source records attributed to A Bergqvist.

At least 37 records · Page 2Linked to original sources
PubMed1999

Divergent effects of weight reduction and oral anticonception treatment on adrenergic lipolysis regulation in obese women with the polycystic ovary syndrome.

The influence of weight reduction and female sex hormones on the regulation of lipolysis was investigated in isolated abdominal sc adipocytes from 20 obese hyperandrogenic women with polycystic ovary syndrome (PCOS). Nine PCOS women were reinvestigated after 8-12 weeks of weight reduction therapy (WR) with a very low calorie diet, inducing a mean loss of 8 +/- 3 kg, and 8 PCOS women were reinvestigated after 12 weeks of treatment with combined oral contraceptives (OC), containing ethinyl estradiol and norethisterone; the remaining 3 subjects were drop-outs. Both WR and OC normalized hyperandrogenicity. WR caused a 50% reduction of basal lipolysis rate and a 5- to 7-fold increased noradrenaline and terbutaline sensitivity (P < 0.02); the latter could be ascribed to a 2-fold increased beta2-adrenoceptor density (P < 0.02) as determined with radioligand binding. There was no change with regard to dobutamine (beta1-adrenoceptor sensitivity) or clonidine, (alpha2-adrenoceptor sensitivity) or to beta1-adrenoceptor density. OC treatment did not influence the basal lipolysis rate or beta2- or alpha2-adrenoceptor sensitivity, but lowered the beta1-adrenoceptor sensitivity 7-fold (P < 0.03) without a reduction in beta1-adrenoceptor density. The OC treatment effect was not observed when forskolin and dibutyryl cAMP, acting on adenylate cyclase or protein kinase A, respectively, were used, suggesting a partial uncoupling of beta1-adrenoceptors. WR therapy, but not OC therapy, caused, in addition to changes in lipolysis function, improved in vivo insulin sensitivity and lower plasma noradrenaline levels. These findings suggest that factors other than hyperandrogenicity modulate lipolysis regulation in obese subjects with PCOS. Disturbances in sympathetic pathways could be of pathogenic importance.

Adipocytes↗
PubMed1999

Current drug therapy recommendations for the treatment of endometriosis.

The principal symptoms and signs of endometriosis are tissue lesions and pelvic pain. These occur to varying degrees, with a chronic pattern and a tendency for deterioration with time. Patients with endometriosis often also have fertility problems, but the relationship between this and the signs and symptoms of the disease is inconsequent; the basic pathophysiology is not exactly known. Although an immunological defect resulting in an inflammatory reaction around discharged menstrual debris in the pelvic cavity has been shown, no treatments based on this process are available. Estrogen often plays an important role in the progression of lesions and pain. Therefore, the aim of treatment usually has been to downregulate the ovaries and/or given antiestrogenic drugs as an alternative to surgical removal. As complete downregulation of the ovaries and hypoestrogenaemia does not seem to be crucial, achievement of amenorrhoea seems to be sufficient. This means that women may continue to have circulating estrogen levels so that severe hypoestrogenic adverse effects such as bone demineralisation, dry vagina, psychiatric symptoms or anabolic/androgenic effects of gestagens can be avoided. However, as both symptoms and the dependence of hormones may vary between and within women, the treatment needs to be individualised. There are a number of available treatments for endometriosis on the market and it is important for the doctor to know how to reach the therapeutic window of these treatments for each woman. It is also important to inform the patient about the different possibilities so that the treatment with the least impact on her quality of life can be chosen. When the therapeutic window has been identified, the treatment may then either be continued for a long period of time or be repeated when needed.

Endometriosis↗
PubMed1998

Effects of triptorelin versus placebo on the symptoms of endometriosis.

OBJECTIVE: To compare the effect of a GnRH-agonist, triptorelin, versus placebo on the symptoms of endometriosis. DESIGN: A prospective, randomized, double-blind study of 6 months of treatment followed by 12 months of follow-up. SETTING: Departments of Obstetrics and Gynecology at two universities and one general hospital. PATIENT(S): Forty-nine women with symptoms of laparoscopically verified endometriosis. INTERVENTION(S): Triptorelin depot or placebo was given every 4 weeks. Clinical evaluation, including the Duration Intensity Behavior Scale and Visual Analogue Scale for pain, was performed before the injections and up to 12 months after treatment. A control laparoscopy was performed 4-6 weeks after the last injection. MAIN OUTCOME MEASURE(S): Quantitation of pain. RESULT(S): Twenty-four patients had active treatment and 25 received placebo. Pain symptoms according to both scales were significantly more reduced after 2 months of triptorelin treatment compared to placebo. The extent of endometriotic lesions was reduced 50% during triptorelin treatment and increased 17% during placebo. The average area of endometriotic lesions was reduced 45% during triptorelin treatment but was unchanged during placebo. Side effects, mainly hot flushes, were experienced by 80% of the actively treated group but also by 33% of patients in the placebo group. Because of recurrent symptoms, only five patients could be observed for 12 months after completion of treatment. CONCLUSION(S): Triptorelin reduces endometriotic lesions and pain to a significantly higher degree than placebo.

Adult↗
PubMed1998

Fibrinolytic factors in endometriotic tissue, endometrium, peritoneal fluid, and plasma from women with endometriosis and in endometrium and peritoneal fluid from healthy women.

OBJECTIVE: To determine whether there is a difference in fibrinolytic compounds in endometriotic tissue, endometrium, peritoneal fluid (PF), and plasma from women with endometriosis and in endometrium and PF from healthy women. DESIGN: Prospective study. SETTING: Two university clinics. PATIENT(S): Regularly menstruating women with and without endometriosis. INTERVENTION(S): Tissue samples, PF, and blood were collected at surgery performed for clinical reasons. MAIN OUTCOME MEASURE(S): The antigen concentrations of plasminogen activators and plasminogen activator inhibitors (PAls) in tissue homogenates, PF, and plasma were assayed by ELISA. RESULT(S): The concentrations of urokinase plasminogen activator (u-PA) and PAI-1 were higher in endometrium from women with endometriosis than in endometrium from controls and even higher in endometriotic tissue than in endometrium from both groups. In PF, the concentration of PAI-2 was higher in women with endometriosis than in controls. CONCLUSION(S): The high concentrations of u-PA and PAI-1 in endometrium from women with endometriosis might facilitate implantation of endometrial cells and the high concentration in endometriotic tissue might contribute to their invasive growth. The inflammatory reaction may contribute to the high concentration of PAI-2.

Adult↗
PubMed1998

Outcome of IVF in patients with endometriosis in comparison with tubal-factor infertility.

PURPOSE: The aim of this retrospective study was to compare the outcome of in vitro fertilization and embryo transfer in women with endometriosis and a control group with tubal-factor infertility. METHODS: Forty-eight patients with endometriosis underwent 65 cycles of in vitro fertilization and embryo transfer at Huddinge University Hospital. The matched control group with tubal-factor infertility consisted of 98 cycles in 98 patients. These groups were retrospectively analyzed regarding stimulation, fertilization, embryo development, implantation, and pregnancy outcome. RESULTS: The fertilization rate was significantly lower in women with endometriosis, but the cleavage, implantation, and pregnancy rates did not differ. CONCLUSIONS: Our results show that women with endometriosis have a lower fertilization rate compared with women with tubal-factor infertility. However, once the oocyte is fertilized, it seems that the preembryo has a normal chance of implantation, leading to similar pregnancy rates.

Adult↗
PubMed1998

Template-dependent initiation of Sindbis virus RNA replication in vitro.

Recent insights into the early events in Sindbis virus RNA replication suggest a requirement for either the P123 or P23 polyprotein, as well as mature nsP4, the RNA-dependent RNA polymerase, for initiation of minus-strand RNA synthesis. Based on this observation, we have succeeded in reconstituting an in vitro system for template-dependent initiation of SIN RNA replication. Extracts were isolated from cells infected with vaccinia virus recombinants expressing various SIN proteins and assayed by the addition of exogenous template RNAs. Extracts from cells expressing P123C>S, a protease-defective P123 polyprotein, and nsP4 synthesized a genome-length minus-sense RNA product. Replicase activity was dependent upon addition of exogenous RNA and was specific for alphavirus plus-strand RNA templates. RNA synthesis was also obtained by coexpression of nsP1, P23C>S, and nsP4. However, extracts from cells expressing nsP4 and P123, a cleavage-competent P123 polyprotein, had much less replicase activity. In addition, a P123 polyprotein containing a mutation in the nsP2 protease which increased the efficiency of processing exhibited very little, if any, replicase activity. These results provide further evidence that processing of the polyprotein inactivates the minus-strand initiation complex. Finally, RNA synthesis was detected when soluble nsP4 was added to a membrane fraction containing P123C>S, thus providing a functional assay for purification of the nsP4 RNA polymerase.

Animals↗
PubMed1997

Cancer risk after a hospital discharge diagnosis of endometriosis.

OBJECTIVES: Our goal was to determine the risk of cancer after hospitalization for endometriosis. STUDY DESIGN: Records of 20,686 women hospitalized with endometriosis during the period 1969 to 1983, as identified through the nationwide Swedish Inpatient Register, were linked against the National Swedish Cancer Registry through 1989 to identify all subsequent diagnoses of cancer. The study subjects were followed up for a mean of 11.4 years, with the cohort contributing 216,851 woman years of follow-up. Standardized incidence ratios were computed by the use of age- and period-specific incidence rates derived from the Swedish population. Because of the high proportion of subjects with gynecologic operations (55.6%), evaluation of the risk of gynecologic cancers involved truncation of person years at the time of any such operation. RESULTS: The overall cancer risk was 1.2 (95% confidence interval 1.1 to 1.3). Significant excesses were observed for breast cancer (standardized incidence ratio = 1.3, 95% confidence interval 1.1 to 1.4), ovarian cancer (1.9, 1.3 to 2.8), and hematopoietic malignancies (1.4, 1.0 to 1.8); this latter excess was largely driven by an excess risk of non-Hodgkin's lymphoma (1.8, 1.2 to 2.6). The risk of ovarian cancer was particularly elevated among subjects with a long-standing history of ovarian endometriosis (4.2, 2.0 to 7.7). Cervical cancer risk was slightly reduced (0.7, 0.4 to 1.3) whereas no association was observed for cancer of the endometrium (1.1, 0.6 to 1.9). CONCLUSIONS: These findings suggest that further attention be given to the risk of breast, ovarian and hematopoietic cancers among women with endometriosis and to exploring possible hormonal and immunologic reasons for the excess risks.

Breast Neoplasms↗
PubMed1997

Concentrations of prostaglandin F2alpha in follicular fluid from women with endometriosis.

Previous data have indicated that prostaglandins (PG) play an important role in the ovulation process and significant quantities have been found in follicular fluid. The synthesis of PG is influenced by ovarian steroids as well as inflammatory processes. Increased PG has been shown in peritoneal fluid from women with endometriosis. The aim of this study was to see whether PGF2alpha concentration in follicular fluid varies according to the presence or absence of remaining endometriotic lesions in the pelvis of women with endometriosis. Follicular fluid was collected at visual puncture of the follicles at laparoscopy of 26 women with diagnosed endometriosis. Visible lesions were found in 10 women and in 16 women no lesions could be seen macroscopically. PGF2alpha was determined using radioimmunoassay. The results showed no significant difference in the concentrations of PGF2alpha between women with visible and not macroscopically visible endometriotic lesions and there was no significantly linear correlation with endometriotic lesions in the follicle punctured. These data are in accordance with clinical results showing that fertility rate does not increase in endometriotic women even if the lesions disappear after treatment.

Adult↗
PubMed1997

Detection of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis: a comparison of the alkaline phosphatase and immunofluorescent techniques.

BACKGROUND: The reported prevalence of antineutrophil cytoplasmic antibodies (ANCA) in primary sclerosing cholangitis (PSC) varies considerably (26-85%). Part of this may reflect methodological differences but part may reflect the differences in the patient groups analysed. To resolve this issue we compared the sensitivity and specificity of the immunoalkaline phosphatase (IALP) and immunofluorescence (IF) techniques in four different populations. METHOD: Sera from four centres were tested blind on alcohol-fixed neutrophils using both techniques. PATIENTS: USA: 14 PSC, 14 primary biliary cirrhosis (PBC); Sweden: 32 PSC, 3 autoimmune hepatitis (AIH), 14 PBC, 11 chronic liver disease; Norway: 32 PSC, 14 AIH, 13 PBC, 1 hepatitis C. Italy: 8 PSC, 14 PBC, 8 viral hepatitis. Thirty-six normal healthy volunteers from Oxford, together with positive and negative controls, were also tested. RESULTS: The healthy controls were all ANCA negative. The diagnostic sensitivity and specificity, respectively, of ANCA for PSC using the IALP technique for the different test sera were: USA 71% and 93%, Sweden 66% and 96%, Norway 69% and 46%, Italy 50% and 95%. The diagnostic sensitivity and specificity, respectively, of the IF technique on the same sera were: USA 50% and 86%, Sweden 56% and 86%, Norway 47% and 61%, Italy 50% and 91%. Overall, combining all four groups, detection of ANCA using the IALP technique gave a diagnostic sensitivity of 66% with a specificity of 74% for PSC. In contrast, the IF technique gave an overall diagnostic of only 51% (P = 0.044, compared with IALP) with a specificity of 73%. Although overall the IALP technique was more sensitive than IF, the differences in sensitivity and specificity between the two techniques did not reach statistical significance for any individual group. Furthermore, the small differences in sensitivity between the four groups using either technique were not significant. However, the IALP technique had greater specificity in the US, Swedish and Italian groups compared with the Norwegian group (P < 0.05) whereas no statistically significant differences in specificity were noted between the groups using the IF technique. CONCLUSION: This study shows that the IALP method of ANCA detection is at least as sensitive as IF for the serological diagnosis of PSC. Indeed, combining data from all four centres, the IALP technique was significantly more sensitive than IF. We therefore recommend the use of the IALP technique, which is also easier to interpret and does not require the use of a specialist fluorescent microscope. The lack of a wide variation in sensitivity between IALP and IF for any individual patient group reported in this study suggests that the previously reported regional differences in ANCA prevalence in PSC of between 26% and 85% may be patient, related, rather than due to ethnic or methodological differences in ANCA detection, perhaps reflecting possible disease heterogeneity within PSC, or case selection bias. Further studies are needed to investigate this intriguing possibility. Such differences, if confirmed, will need to be taken into account when assessing the use of ANCA as a serological marker of PSC.

Adult↗
PubMed1997

Altered susceptibility to tumor necrosis factor alpha-induced apoptosis of mouse cells expressing polyomavirus middle and small T antigens.

Infection with some virus types induces susceptibility to the cytotoxic effect of tumor necrosis factor alpha (TNF-alpha). To investigate whether expression of polyomavirus proteins has this effect on cells, the TNF-alpha sensitivity of C127 and L929 mouse cells transfected with viral DNA was analyzed. Expression of all three polyomavirus early proteins, the tumor (T) antigens, had no apparent effect. In contrast, middle T antigen by itself induced hypersensitivity to TNF-alpha. This effect was reversed by retransfection of the cells with DNA encoding small T antigen. Expression of this polypeptide also decreased the sensitivity of bovine papillomavirus type 1-transformed cells to TNF-alpha, showing that the protective function of the polyomavirus small T antigen was not strictly linked to a middle-T-antigen-induced event. Mouse and human TNF-alpha had the same effect on normal and transformed mouse cells, suggesting that this effect was mediated by TNF receptor 1. Consistent with this conclusion, all cell clones used in the experiments expressed TNF receptor 1 at similar levels, while we failed to detect TNF receptor 2. The amount of receptor on the cells was not influenced by binding of the ligand. Addition of TNF-alpha at cytotoxic concentrations to cells expressing middle T antigen by itself resulted in significant fragmentation of chromosomal DNA after only a few hours, indicating induction of apoptosis. Addition of the cytokine to these cells also leads to release of arachidonic acid, showing that phospholipase A2 was activated. However, production of arachidonic acid did not appear to significantly precede loss of cell viability.

Animals↗
PubMed1997

Quantitative enzyme immunoassay and semiquantitative immunohistochemistry of oestrogen and progesterone receptors in endometriotic tissue and endometrium.

BACKGROUND: The capacity of different tissues to respond to steroids has been evaluated mainly according to the concentrations of oestrogen (ER) and progesterone (PR) receptors, which may be assayed either in tissue homogenates or histochemically. These two principles have been used in different studies of endometriotic tissue, giving somewhat different results, probably because the tissue is heterogeneously mixed with fibrotic tissue and blood cells to various degrees. AIMS: To compare a quantitative and a qualitative, semiquantitative immunocytochemical assay for ER and PR in a heterogenous tissue (endometriotic) and a similar but more homogenous tissue (endometrium). METHODS: ER and PR concentrations were measured using enzyme immunoassay (EIA) and immunocytochemistry (ICA) in the same tissue samples (endometriotic tissue from 31 women and endometrium from 19 of the same women). RESULTS: There was a significant correlation between PR concentration (using EIA) and semiquantitation of PR using PRICA in endometrial epithelium (p = 0.028). The correlation between the two techniques for ER concentration was not significant. In endometriotic tissue no correlation was found between the two techniques for ER or PR. CONCLUSIONS: These data show that in heterogeneous tissues like endometriotic tissue different techniques for measuring steroid receptors may produce substantially different results. The two techniques (EIA and ICA) are complementary and a combination of the two techniques might aid in determining optimal treatment.

Adult↗
PubMed1997

Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance?

The polycystic ovary syndrome (PCOS) is the most common hyperandrogenic disorder among women and is characterized by metabolic and cardiovascular aberrations similar to those seen in the so-called insulin resistance syndrome. The regulation of lipolysis was investigated in isolated abdominal sc adipocytes from 10 nonobese women with PCOS and in 11 age- and body mass index-matched healthy women. Eight PCOS women were reinvestigated after 3 months of treatment with combined oral contraceptives containing ethinyl estradiol and norethisterone, which normalized hyperandrogenicity. The PCOS women showed a marked resistance to the lipolytic effect of noradrenaline due to defects at two different levels in the lipolytic cascade: first, a 7-fold reduction in sensitivity to the beta 2-selective agonist terbutaline (P < 0.005), which could be ascribed to a 50% lower beta 2-adrenoceptor density (P < 0.02) as determined with radioligand binding; there was no difference with regard to dobutamine (beta 1) or clonidine (alpha 2-sensitivity) or beta 1-adrenoceptor density; second, the maximum lipolytic response was also 35% lower (P < 0.02) in the PCOS women compared to that in the healthy women. This was seen with all beta-adrenergic agonists and the postreceptor-acting agents forskolin (activating adenylyl cyclase) and dibutyryl cAMP (activating protein kinase). Neither beta 2-adrenoceptor sensitivity or density nor the reduced lipolytic responsiveness was restored by 3 months of oral contraceptives treatment. The results indicate the existence of a marked impairment of catecholamine-induced lipolysis in nonobese PCOS women displaying early features of the insulin resistance syndrome due to multiple lipolysis defects as a lower beta 2-adrenoceptor density and reduced function of the protein kinase, hormone-sensitive lipase complex. These lipolysis defects are identical to those observed in the insulin resistance (metabolic) syndrome and could be a primary pathogenic mechanism for the development of these disorders.

Adipocytes↗
PubMed1997

A double-blind randomized study of the treatment of endometriosis with nafarelin or nafarelin plus norethisterone.

The objective of this study was to compare the efficacy of nafarelin 200 micrograms (Group A), nafarelin 400 micrograms (Group B) and the combination of nafarelin 200 micrograms and norethisterone 1.2 mg (Group C) daily, in treating symptoms of endometriosis, American Fertility Society score and adverse events during 6 months of treatment. A prospective, randomized, double-blind parallel group study was performed in two centers and 49 women with endometriosis diagnosed laparoscopically were included. The patients were seen monthly for physical examination and records were taken for bleeding pattern, symptom score and adverse events. A control laparoscopy was performed at the end of 6 months of treatment. All patients were followed 6 months after treatment. At 3 and 6 months the pelvic examination total score had decreased significantly in all three groups. The total endometriosis score was significantly reduced in Groups B and C. After 2 months the total symptom score showed a significant decrease in Groups B and C. The frequency of hot flushes during the first month of treatment was lowest in Group C, but during the rest of treatment there were no differences between the groups. Best bleeding control was obtained in Group C. We conclude that nafarelin 200 micrograms daily has as good an effect on endometriosis symptoms as nafarelin 400 micrograms daily, and the addition of norethisterone 1.2 mg results in fewer hot flushes and better bleeding control.

Adult↗
PubMed1996

Integrins alpha 3 and alpha 6 are differentially expressed in endometrium and endometriosis.

The expression of integrin subunits has been investigated in the stroma and epithelium of eutopic and ectopic endometrial tissues, using immunohistochemistry and fluorescently activated cell-sorting techniques. Integrin subunits exhibited tissue-specific expression in both eutopic and ectopic endometrium. Integrin alpha 3 subunit was up-regulated in ectopic endometrium compared with the eutopic counterpart, whereas alpha 6 integrin subunit was down-regulated in the ectopic tissues. Cycle stage-dependent expression of alpha v and beta 3, observed in eutopic endometrium, was absent in the ectopic counterpart. It is concluded that the development and regeneration of the endometrium involve complex integrin-ligand interactions and that regulation of specific adhesive events is lost in endometriosis.

Adult↗
PubMed1996

Flow cytometric DNA analysis in endometriotic tissue compared to normal uterine endometrium.

Endometriotic tissue sometimes shows an invasive pattern. but the growth regulation of the tissue is insufficiently characterized. In a research programme on factors regulating endometriotic growth, the DNA ploidy status and S-phase fraction (SPF) were studied. Fresh-frozen endometriotic tissue from 14 women and endometrium from 11 of them were studied using flow cytometry. A clear diploid pattern was seen in most cases of endometriotic (8/14) and endometrial (8/11) samples. In the remaining cases the G0/G1 peak was broad and skewed, which might indicate a near-diploid cell population. To clarify this, a second group was studied, consisting of 29 formalin-fixed endometriotic samples from 22 women and endometrium from five of them. All these samples were diploid, with one having a broad G0/G1 peak. No convincing difference in SPF between endometrium and endometriotic tissue was found, as the calculations had to be handled with caution because of debris in many samples. Although the study of fresh-frozen samples gave some indications of differences in DNA ploidy status, flow of cytometric DNA analysis of formalin fixed samples of endometriosis showed a diploid DNA pattern in all samples. In conclusion, DNA flow cytometry did not show a convincing aneuploid DNA pattern in endometriotic tissue.

DNA↗
PubMed1996

A comparison of cathepsin D levels in endometriotic tissue and in uterine endometrium.

OBJECTIVE: To assay the cathepsin D level in endometriotic tissue, to study the difference to uterine endometrium and the correlation to localization. DESIGN: Prospective consecutive study on endometriotic tissue and endometrium. SETTING: University clinic. PATIENTS: Thirty-five women undergoing laparotomy for clinical indications. INTERVENTIONS: Samples of endometriotic tissue and uterine endometrium were obtained simultaneously from the same woman at laparotomy, fresh frozen, and assayed using an immunoradiometric method. MAIN OUTCOME MEASURE: The cathepsin D level in endometrium and endometriotic tissue expressed in pmol/mg DNA. RESULTS: The cathepsin D level was significantly higher in endometriotic tissue than in endometrium both in follicular and luteal phase. The highest values in endometriotic tissue were found in luteal phase, in ovarian lesions, and in primary lesions. In endometrium, but not in endometriotic tissue, there was a positive correlation between cathepsin D level and serum E2 level. CONCLUSION: The level of the proteolytic enzyme cathepsin D is significantly higher in endometriotic tissue than in endometrium, which might be of importance for implantation and the invasive growth of endometriotic tissue.

Cathepsin D↗
PubMed1994

Apoptosis of Spodoptera frugiperda cells induced by okadaic acid is abrogated by baculovirus infection.

Okadaic at low concentrations specifically inhibits protein phosphatase 2A. Treatment of cells with this inhibitor leads to growth arrest and cell injury within 1 to 2 days. After testing several different types of cells we found that mouse 3T6 cells and insect Sf9 cells responded to okadaic acid by apoptosis, as defined by changes in morphology and degradation of chromatin to fragments of nucleosome size. Infection of insect cells by baculovirus prevented the okadaic acid-induced apoptosis. Analysis of phosphoprotein synthesis by polyacrylamide gel electrophoresis showed that okadaic acid treatment resulted in hyperphosphorylation of some cellular proteins, including histone H1. Concomitant baculovirus infection of the cells did not change the overall phosphorylation pattern, but appeared to mitigate the okadaic acid-induced hyperphosphorylation of histone H1.

Animals↗