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Biomedical subjects

D K Sen

Publications and source records attributed to D K Sen.

At least 19 recordsLinked to original sources

Serum alpha-1 acid glycoprotein levels in patients with idiopathic peripheral retinal vasculitis (Eales' disease).

Serum alpha-1 acid glycoprotein levels were measured in 27 patients with idiopathic peripheral retinal vasculitis (Eales' disease) and 31 healthy subjects by single radial immunodiffusion technique. The levels were found to be significantly increased in both moderate and severe types of the disease. The serum levels of this protein paralleled the severity of the disease. The increased alpha-1 acid glycoprotein in serum showed a significant fall to near normal levels during the quiescent stage. Our observations support the hypothesis that idiopathic peripheral retinal vasculitis is an immune mediated disease. It is proposed that serum alpha-1 acid glycoprotein may be considered as a reliable parameter of the activity and the degree of severity of the disease, as well as an useful tool for monitoring the efficacy of treatment.

Adolescent

Plasminogen activators t-PA, u-PA and its inhibitor (PAI) in normal males and females.

We determined the plasma levels of tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) activity and their antigen levels including urokinase plasminogen activator (u-PA) in 33 male and 27 female normal subjects. Males had mean t-PA activity of 0.50 iu/ml which was significantly lower (p less than 0.01) than the females 0.64 iu/ml. Males had higher (p less than 0.001) mean PAI activity (15.5 AU/ml) as compared to females 10.3 AU/ml. The respective mean levels of t-PA and PAI antigen were significantly higher (p less than 0.01) in males (8.1 ng/ml and 17.6 ng/ml) than in females (6.2 ng/ml and 12.1 ng/ml). The mean u-PA level in males was 1.54 ng/ml which was significantly higher (p less than 0.01) than in females with 1.02 ng/ml. In post-venous occlusion studies, females had a greater mean response of 8.6 fold in t-PA activity as compared to males with a mean of 4.5 fold increase. The mean t-PA antigen response in males was 2.0 fold increase as compared to 2.6 fold increase in the females. No significant responses were seen in both sexes in either PAI activity or antigen levels when compared with the resting state. In zymography studies, free t-PA, its inhibitor complexes and u-PA were demonstrated in the euglobulin fractions of stored plasma. This study demonstrates that significant differences in t-PA, u-PA and PAI exist between male and female subjects which should be taken into account when determining their levels in clinical conditions.

Adult

Serum beta-2 microglobulin level in sympathetic ophthalmitis.

Serum beta-2 microglobulin (beta 2-m) levels were measured in 12 patients with sympathetic ophthalmitis, 34 with neglected traumatic uveitis following penetrating injury and 36 healthy subjects by ELISA technique. There was no significant alteration of its level in patients with traumatic uveitis. However, its levels were significantly increased in patients with sympathetic ophthalmitis. They were high even in the early stage of the disease. Serum beta 2-m levels paralleled the severity of disease. It decreased significantly at the remission stage. Four patients came back with relapse of the condition and the level of serum beta 2-m was again found to be elevated in them. It is proposed that estimation of beta 2-m can be used as a diagnostic aid when the diagnosis of sympathetic ophthalmitis remains doubtful on clinical grounds. It is also suggested that a rise in serum beta 2-m in patients with traumatic uveitis following perforating injuries may point to the onset of sympathetic ophthalmitis. The extent of rise in its level may be considered a good parameter of the degree of severity of sympathetic ophthalmitis. It may also act as a useful tool to evaluate the drug efficacy in this disease and predict relapse.

Acute Disease

Evidence for several fold more activity of NAD+-dependent uterine prostaglandin 15-hydroxydehydrogenase in transsexual than in non-transsexual women.

The activity of NAD+-dependent PGDH was measured in the cytosolic fractions (100,000 x g) of uterine tissues obtained from transsexual, pregnant and non-pregnant women. The specific activity (mean +/- SD) of the enzyme at maximum velocity of the enzyme reaction in these three groups of women was 5.5 +/- 2.30, 0.53 +/- 0.27 and 0.54 +/- 0.25 mU/mg protein respectively using PGE2 as substrate, and with PGF2 alpha as substrate the respective values were 5.48 +/- 2.80, 0.49 +/- 0.41 and 0.51 +/- 0.30 mU/mg protein. These data suggest that, with either substrate, the uterine enzyme activity in the transsexuals was about 10-fold greater than in pregnant and non-pregnant women (p less than 0.001). However, the Km values of the enzyme for both PGE2 and PGF2 alpha were similar in all three groups, indicating the presence of same enzyme in the uterus of transsexual, pregnant and non-pregnant women. We speculate that PGDH activity was raised in the uterus of transsexual women because of the prolonged androgen therapy they received for the management of female-to-male transsexualism.

Adult

A plasmin generation method for the determination of tissue plasminogen activator (t-PA) activity in blood.

A plasmin generation method to determine tissue plasminogen activator (t-PA) activity in plasma is described. A protein solution of homogenized fibrin was used as a stimulator in the presence of plasminogen and the plasmin generated was measured by the release of para-Nitroanilide (p-NA) from the chromogenic substrate S-2251. Plasmin generation by 5 iu/mL t-PA in the presence of 1 CU/mL of plasminogen and 850 micrograms/mL of fibrin solution reaches a peak at about 5 h incubation whilst in plasma, plasmin generation peaks after about 16 h incubation. The highest t-PA activity in plasma was determined using an assay involving 18 h incubation. In the 21 subjects studied by this method the t-PA activity at rest ranged from 0.34 to 0.92 iu/mL with a mean of 0.57 +/- 0.15 iu/mL of plasma whilst in the post-occlusion state the activity ranged from 1.12 to 18.0 iu/mL, with a mean of 5.25 +/- 4.49 iu/mL of plasma. We also found that subjects who developed petechiae during occlusion had significantly higher t-PA activity both at pre- and post-occlusion when compared with those who did not develop petechiae. The t-PA activity of acid-treated plasma stored at -70 degrees C showed no significant changes in activity after 12 weeks of storage when compared with the t-PA activity of the same plasma tested prior to storage.

Adult

Prostaglandin 15-hydroxydehydrogenase activity in human penile corpora cavernosa and its significance in prostaglandin-mediated penile erection.

Prostaglandins may be involved in human penile erection and erectile failure. To evaluate the possible role of prostaglandin metabolism in the penile tissue, the activity of nicotinamide adenine dinucleotide-dependent prostaglandin 15-hydroxydehydrogenase was assayed in the corpora cavernosa of the human penis. Km values (mean +/- SD) of the enzyme for PGE1, PGE2 and PGF2 alpha were 60.1 +/- 4.2, 17.7 +/- 1.5 and 16.1 +/- 1.2 microM respectively; Vmax values (mean +/- SD) were 0.219 +/- 0.062, 0.510 +/- 0.012 and 0.424 +/- 0.007 nmol/min/mg protein respectively. The implications of these findings in the erectile process are discussed.

Humans

Serum beta-2 microglobulin level in acute idiopathic anterior uveitis.

Serum beta-2 microglobulin levels were measured in 68 patients with acute idiopathic anterior uveitis and 51 healthy subjects by ELISA technique. The levels were found to be significantly increased in moderate and severe types of uveitis despite a normal renal glomerular function in all patients. The parameters remained unaltered in mild types. Serum beta-2 microglobulin levels closely paralleled the severity of the disease. The increased beta-2 microglobulin level in serum showed a significant fall to normal levels on clinical improvement. The data further strengthen the hypothesis that acute idiopathic anterior uveitis is an immune mediated disease. It is proposed that serum beta-2 microglobulin may be considered as a reliable parameter of the degree of severity of acute idiopathic anterior uveitis, as well as representing a useful tool for the evaluation of drug efficacy, especially in intractable cases.

Acute Disease

Fractionation and characterization of oxytocinases in human semen.

Two isoenzymes of oxytocinase activity were fractionated from human seminal plasma by acrylamide-agarose gel chromatography and partly characterized using S-benzyl-L-cysteine-p-nitroanilide (BCN) and L-leucine-p-nitroanilide (LN) separately as substrates. These isoenzymes appeared to be metallo-aminopeptidases with different elution volumes (90 ml and 150 ml), apparent molecular weights (unknown value and 300,000) and pH optima (6.8 and 7.0 with BCN and 7.2 and 7.4 with LN), but with similar substrate affinity and thermal sensitivity, and susceptibility to EDTA, divalent metal ions, L-methionine, polypeptide hormones and prostaglandins. A comparison of the enzymic properties with pregnancy-associated oxytocinases suggests that seminal oxytocinases are related more closely to amniotic fluid isoenzymes than to pregnancy serum, placental and uterine isoenzymes.

Aminopeptidases

Immature teratoma of the ovary.

Results of treatment of 9 cases of pure immature teratoma of the ovary seen at the University Hospital, Kuala Lumpur, are presented. Six patients were in Stage 1 and three in Stage 3. A majority of them had grade 2 or 3 tumors. Four patients in Stage 1 had the conservative surgery of salpingo-oophorectomy performed, the more radical procedure of total hysterectomy, bilateral salpingo-oophorectomy omentectomy, and tumor debulking where feasible being carried out in the others. Adjuvant chemotherapy consisted of either pulsed cyclophosphamide, VAC (vincristine, actinomycin D, and cyclophosphamide) or PVB (cis-platinum, vinblastine, bleomycin) regimes. Seven patients have survived for periods up to 9 years with no clinical evidence of disease.

Adolescent

Adjuvant cytotoxic chemotherapy following Wertheim radical hysterectomy for cervical cancer.

Patients at high risk of recurrence or metastases following radical surgery for Stage 1B and 2A cervical carcinoma include those with pelvic node metastases, lymphatic or vascular space permeation in the cervix by tumour cells, large size of the primary tumour, involvement of the full thickness of the cervix and parametrial spread. We report the initial results of adjuvant chemotherapy using a combination of cisplatinum, bleomycin and vinblastine in 22 patients who had undergone Wertheim radical hysterectomy and were thought to be at high risk of developing recurrence. The mean duration of follow-up was 23 months. All are alive after follow-up ranging from 13 to 43 months. Three patients developed recurrences--one in the pelvis, another at the posterior aspect of the urethral meatus and the third developed pulmonary secondaries at 20 to 23 months after surgery. Toxicity from the chemotherapy was acceptable.

Antineoplastic Combined Chemotherapy Protocols

Cerebral metastases from choriocarcinoma. Results of chemotherapy.

Of 36 cases of choriocarcinoma treated at the University Hospital Kuala Lumpur during 1980-84 inclusive, 6 patients were found to have cerebral metastases. Intrathecal methotrexate and combination chemotherapy were started in all cases, with monitoring of tumor growth by serial beta-HCG assays and CT scanning of brain and lung. Chemotherapy was reduced because of severe toxicity in 2 patients, one of whom received radiotherapy to the brain. Four patients (66%) have now been in remission for 2.5-6 years. Two did not respond to therapy and died. The factors involved in therapy and response are discussed.

Adult

Immunoassay of serum muramidase (lysozyme) in ocular diseases.

Serum levels of muramidase activity were measured in 162 patients with different ocular diseases and 84 healthy subjects by electro-immuno-diffusion technique. We demonstrated for the first time that electro-immuno-diffusion technique could be successfully applied for the estimation of serum muramidase concentrations. Serum muramidase was found to be high in significant number of cases with granulomatous uveitis, tuberculous keratitis, central serous retinopathy and Eales' disease. Tuberculosis was presumed to be the cause in them by the process of exlusion. Patients with high serum muramidase activity were subjected to anti-tubercular treatment with a marked clinical improvement. It is suggested that high serum muramidase could be an useful parameter in deciding the line of treatment in patients with ocular diseases of uncertain etiology. Serum muramidase concentrations showed return to normal levels with the clinical improvement of the diseases with treatment. It increased again with the re-appearance of the activity of the diseases.

Eye Diseases

Serum fibrin degradation products in acute idiopathic anterior uveitis.

Levels of serum fibrin degradation products were measured by the Staphylococcal clumping test in patients with acute idiopathic anterior uveitis and traumatic anterior uveitis. We found them to be significantly increased (P less than 0.001) in patients with acute idiopathic anterior uveitis (11.0 micrograms/ml). The extent of this increase in the serum levels of fibrin degradation products correlated well with increased severity of the disease. It showed return to normal levels (5.0 micrograms/ml) with the clinical improvement. It increased again with the re-appearance of acute stage of the disease. We found no alteration in the levels of serum fibrin degradation products in patients with traumatic anterior uveitis. We hypothesise that uveal deposition of immune complexes causes secondary platelet damage and intravascular coagulation which results in uveal tissue damage through inflammation.

Acute Disease

Biological variations of lysozyme concentration in the tear fluids of healthy persons.

Concentration of tear lysozyme was measured in healthy Indian subjects of the same racial group aged 2 to 78 years by a single radial immunodiffusion technique. Variations in its concentration between the two eyes, during the day, over a period of time, in both sexes, and in different age groups were studied. The diurnal and age-related changes in the concentration of tear lysozyme were found to vary to an appreciable extent. The mean lysozyme concentration in tears was lower in the morning and higher in the evening. It tended to be low in children under 16, rose and attained a plateau in the age group 16-45 years and fell in later life, though still remaining higher than in the children.

Adolescent